Trial Outcomes & Findings for An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia (NCT NCT02180724)

Last Updated: 2025-11-26

Results Overview

ORR defined as the rate of subjects achieving a Miner Response (MR) or better including complete response (CR), very good partial response (VGPR), partial response (PR) and MR; The definition of responses are evaluated by investigators using both Modified 6th criteria (refer to protocol table 4-2 , 4-3) and Modified 3rd International Workshop of Waldenström Macroglobulinemia (IWWM) criteria (refer to protocol table 4-4 and table 4-5 for definition). For Modified 6th criteria, MR is defined as (1) monoclonal IgM protein is detectable, (2) no new signs or symptoms of active disease, (3) and patient has \>=25% but \< 50% reduction in serum monoclonal IgM level from baseline. PR and VGPR both require (1) and (2) as MR, but PR also requires the \>=50% and \<90% reduction in serum monoclonal IgM level as well as reduction in extramedullary disease. VGPR requires \>= 90% reduction in serum IgM and complete resolution of extramedullary disease.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

107 participants

Primary outcome timeframe

Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

Results posted on

2025-11-26

Participant Flow

In the original protocol, previously treated subjects were planned to be randomized 1:1 into 2 cohorts: Cohort 1 to receive Acala 100 mg BID for 28 days and Cohort 2 to receive Acala 200 mg once daily (QD) for 28 days. After enrollment started, the dose regimen was amended. The 200 mg QD dose was eliminated, and subjects who were enrolled under the original protocol and received treatment with 200 mg QD were switched to 100 mg BID.

For the ACE-WM-001 program, Study Terminated by Sponsor refers to the following: Patients receiving treatment benefits will continue to be provided with study medication in the Post Final Analysis Management of the trial. No further data collection for analysis and reporting will be completed after the final Analysis.

Participant milestones

Participant milestones
Measure	Previously Treated (PT) Total PT 100 mg BID + 200 mg QD (N = 92)	Treatment Naive (TN) Cohort 1 TN 100 mg BID (N = 13)
Overall Study STARTED	92	14
Overall Study 200 mg QD	7	1
Overall Study 100 mg BID	85	13
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	92	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Previously Treated (PT) Total PT 100 mg BID + 200 mg QD (N = 92)	Treatment Naive (TN) Cohort 1 TN 100 mg BID (N = 13)
Overall Study Death	26	1
Overall Study Lost to Follow-up	3	1
Overall Study Withdrawal by Subject	4	2
Overall Study PI Decision	5	2
Overall Study Study terminated by sponsor	54	8

Baseline Characteristics

An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Previously Treated (PT) Total n=92 Participants PT 100 mg BID + 200 mg QD (N = 92)	Treatment Naive (TN) Cohort 1 n=14 Participants TN 100 mg BID (N = 13)	Total n=106 Participants Total of all reporting groups
Age, Continuous	68.7 Years STANDARD_DEVIATION 9.8 • n=492 Participants	70.0 Years STANDARD_DEVIATION 13.0 • n=492 Participants	68.9 Years STANDARD_DEVIATION 10.3 • n=984 Participants
Sex: Female, Male Female	29 Participants n=492 Participants	4 Participants n=492 Participants	33 Participants n=984 Participants
Sex: Female, Male Male	63 Participants n=492 Participants	10 Participants n=492 Participants	73 Participants n=984 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=492 Participants	0 Participants n=492 Participants	1 Participants n=984 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	80 Participants n=492 Participants	14 Participants n=492 Participants	94 Participants n=984 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=492 Participants	0 Participants n=492 Participants	11 Participants n=984 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Asian	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Black or African American	2 Participants n=492 Participants	0 Participants n=492 Participants	2 Participants n=984 Participants
Race (NIH/OMB) White	80 Participants n=492 Participants	14 Participants n=492 Participants	94 Participants n=984 Participants
Race (NIH/OMB) More than one race	1 Participants n=492 Participants	0 Participants n=492 Participants	1 Participants n=984 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=492 Participants	0 Participants n=492 Participants	9 Participants n=984 Participants
Region of Enrollment USA	19 participants n=492 Participants	9 participants n=492 Participants	28 participants n=984 Participants
Region of Enrollment United Kingdom	50 participants n=492 Participants	5 participants n=492 Participants	55 participants n=984 Participants
Region of Enrollment Netherlands	7 participants n=492 Participants	0 participants n=492 Participants	7 participants n=984 Participants
Region of Enrollment Italy	5 participants n=492 Participants	0 participants n=492 Participants	5 participants n=984 Participants
Region of Enrollment Greece	3 participants n=492 Participants	0 participants n=492 Participants	3 participants n=984 Participants
Region of Enrollment France	8 participants n=492 Participants	0 participants n=492 Participants	8 participants n=984 Participants

PRIMARY outcome

Timeframe: Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

Population: In the original protocol, previously treated subjects were planned to be randomized 1:1 into 2 cohorts: Cohort 1 to receive Acala 100 mg BID for 28 days and Cohort 2 to receive Acala 200 mg once daily (QD) for 28 days. After enrollment started, the dose regimen was amended. The 200 mg QD dose was eliminated, and subjects who were enrolled under the original protocol and received treatment with 200 mg QD were switched to 100 mg BID. Results are combined.

Outcome measures

Outcome measures
Measure	Previously Treated (N=92) n=92 Participants 100 mg BID N=87 + 200 mg QD N= 5	Treatment Naive (N=14) n=14 Participants 100 mg BID N= 13 + 200 mg QD N=1
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria VGPR (6th IWWM criteria)	21 Participants	0 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria ORR 6th IWWM criteria (CR+VGPR+PR+MR)	87 Participants	13 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria CR (6th IWWM criteria)	4 Participants	0 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria PR (6th IWWM criteria)	52 Participants	10 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria MR (6th)	10 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

Outcome measures

Outcome measures
Measure	Previously Treated (N=92) n=92 Participants 100 mg BID N=87 + 200 mg QD N= 5	Treatment Naive (N=14) n=14 Participants 100 mg BID N= 13 + 200 mg QD N=1
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria ORR 3rd IWWM criteria (CR+VGPR+PR+MR)	87 Participants	13 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria CR (IWWM 3rd criteria)	2 Participants	0 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria VGPR (IWWM 3rd criteria)	38 Participants	1 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria PR (IWWM 3rd criteria)	35 Participants	10 Participants
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria MR (IWWM 3rd criteria)	12 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to approximately 3.8 years. Data cut at last subject have completed Cycle 27 (28 days per Cycle).

Kaplan-Meier (K-M) estimates of the PFS assessments and its 95% confidence interval are provided using both modified 3rd and 6th IWWM criteria by investigator. K-M estimates at a certain time (ex. all subjects complete Cycle 27) provides the estimated percentage of the subjects who are still alive or have not progressed by the given time over all patients at risk. Per 6th IWWM criteria, the progressive disease is defined as \>= 25% increase in serum IgM level with an absolute increase of at least 500 mg/dL from lowest nadir (requires confirmation on at least 2 consecutive measurements at least 4 weeks apart) and/or progression of clinical features attributable to the disease. Per modified 3rd IWWM criteria, besides IgM requirement as 6th criteria, it could also includes progression of clinically significant disease related symptoms and/or death from any cause or initiation of a new anti-neoplastic therapy.

Outcome measures

Outcome measures
Measure	Previously Treated (N=92) n=92 Participants 100 mg BID N=87 + 200 mg QD N= 5	Treatment Naive (N=14) n=14 Participants 100 mg BID N= 13 + 200 mg QD N=1
Progression-free Survival (PFS) of Acalabrutinib by Investigator K-M Point Est. for PFS by 6th IWWM criteria	81.9 percentage of subjects Interval 72.1 to 88.5	90.0 percentage of subjects Interval 47.3 to 98.5
Progression-free Survival (PFS) of Acalabrutinib by Investigator K-M Point Est. for PFS by 3rd IWWM criteria	81.9 percentage of subjects Interval 72.1 to 88.5	90.0 percentage of subjects Interval 47.3 to 98.5

SECONDARY outcome

Timeframe: Primary analysis occur when all subjects have completed Cycle 27 or have discontinued before Cycle 27.

Outcome Measure was pre-specified to summarize data per investigator assessment with respect to subject's vital/survival status is presented in the RRF and irrespective of iWWM 3rd or 6th criteria. Kaplan-Meier (K-M) estimates at a certain time (ex. all subjects complete Cycle 27) provides the estimated percentage of the subjects who are still alive by the given time over all patients at risk.

Outcome measures

Outcome measures
Measure	Previously Treated (N=92) n=92 Participants 100 mg BID N=87 + 200 mg QD N= 5	Treatment Naive (N=14) n=14 Participants 100 mg BID N= 13 + 200 mg QD N=1
Overall Survival (OS) of Acalabrutinib by Investigator	89.0 Percentage of subjects Interval 80.6 to 93.9	90.9 Percentage of subjects Interval 50.8 to 98.7

SECONDARY outcome

Timeframe: Primary analysis occur when all subjects have completed Cycle 27 or have exit the study

DOR is defined as the interval from the first documentation of Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR) or Minor Response (MR) to the earlier of the first documentation of definitive PD or death from any cause. The summary statistics are provided for DOR.

Outcome measures

Outcome measures
Measure	Previously Treated (N=92) n=86 Participants 100 mg BID N=87 + 200 mg QD N= 5	Treatment Naive (N=14) n=13 Participants 100 mg BID N= 13 + 200 mg QD N=1
Summary of Duration of Response (DOR) DOR by Modified 3rd IWWM criteria	21.9 months Standard Deviation 8.1	19.6 months Standard Deviation 8.41
Summary of Duration of Response (DOR) DOR by 6th IWWM Criteria	21.7 months Standard Deviation 8.11	19.5 months Standard Deviation 8.45

Adverse Events

Previously Treated (PT) Cohort 2

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Previously Treated (PT) Total

Serious events: 59 serious events

Other events: 92 other events

Deaths: 26 deaths

Treatment Naive (TN) Cohort 1

Serious events: 9 serious events

Other events: 13 other events

Deaths: 1 deaths

Treatment Naive (TN) Cohort 2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Treatment Naive (TN) Total

Serious events: 9 serious events

Other events: 14 other events

Deaths: 1 deaths

Previously Treated (PT) Cohort 1

Serious events: 56 serious events

Other events: 87 other events

Deaths: 26 deaths

Serious adverse events

Serious adverse events
Measure	Previously Treated (PT) Cohort 2 n=5 participants at risk PT 200 mg QD (n = 5)	Previously Treated (PT) Total n=92 participants at risk PT 100 mg BID + 200 mg QD (N = 92)	Treatment Naive (TN) Cohort 1 n=13 participants at risk TN 100 mg BID (N = 13)	Treatment Naive (TN) Cohort 2 n=1 participants at risk TN 200 mg QD (n = 1)	Treatment Naive (TN) Total n=14 participants at risk TN 100 mg BID + 200 mg QD (n = 14)	Previously Treated (PT) Cohort 1 n=87 participants at risk PT 100 mg BID (n = 87)
Eye disorders Diplopia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Angina pectoris	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiac arrest	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiac failure	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiac failure congestive	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Coronary artery disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Myocardial infarction	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Myocardial ischaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Nodal arrhythmia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Right ventricular failure	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Gastric ulcer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Haematemesis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Asthenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Multiple organ dysfunction syndrome	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Non-cardiac chest pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Pyrexia	20.0% 1/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Bronchitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Covid-19	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Covid-19 pneumonia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Cellulitis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Diverticulitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Empyema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Epiglottitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Gastroenteritis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Infective exacerbation of bronchiectasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 9 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Influenza	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Lower respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.9% 10/92 • Number of events 13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	11.5% 10/87 • Number of events 13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Meningitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Meningitis bacterial	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Neutropenic sepsis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pharyngitis streptococcal	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pneumonia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.0% 11/92 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Prostatitis escherichia coli	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pulmonary sepsis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Rhinovirus infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Rotavirus infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Sepsis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Subcutaneous abscess	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Upper respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Urinary tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Urosepsis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Fall	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Head injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood bilirubin increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood viscosity increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Transaminases increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central nervous system lymphoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma multiforme	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Cerebrovascular accident	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Dizziness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Intracranial haematoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Intracranial mass	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Meningorrhagia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Presyncope	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Seizure	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Syncope	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Acute kidney injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Prostatitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Hypotension	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Orthostatic hypotension	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Vasculitis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.

Other adverse events

Other adverse events
Measure	Previously Treated (PT) Cohort 2 n=5 participants at risk PT 200 mg QD (n = 5)	Previously Treated (PT) Total n=92 participants at risk PT 100 mg BID + 200 mg QD (N = 92)	Treatment Naive (TN) Cohort 1 n=13 participants at risk TN 100 mg BID (N = 13)	Treatment Naive (TN) Cohort 2 n=1 participants at risk TN 200 mg QD (n = 1)	Treatment Naive (TN) Total n=14 participants at risk TN 100 mg BID + 200 mg QD (n = 14)	Previously Treated (PT) Cohort 1 n=87 participants at risk PT 100 mg BID (n = 87)
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.0% 11/92 • Number of events 20 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 20 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Cold type haemolytic anaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Increased tendency to bruise	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.9% 10/92 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.3% 9/87 • Number of events 10 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.7% 20/92 • Number of events 50 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.0% 20/87 • Number of events 50 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 23 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 23 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Blood and lymphatic system disorders Thymic cyst	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Acute coronary syndrome	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Angina pectoris	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Arrhythmia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.7% 8/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	9.2% 8/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Atrial flutter	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Bradycardia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiac amyloidosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiac arrest	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Cardiogenic shock	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Cataract	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Sinus arrhythmia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Supraventricular tachycardia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Cardiac disorders Tachycardia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Deafness unilateral	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Ear congestion	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Ear pain	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Eustachian tube dysfunction	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Excessive cerumen production	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Hyperacusis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Tinnitus	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Tympanic membrane perforation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Ear and labyrinth disorders Vertigo	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Endocrine disorders Hyperparathyroidism primary	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Angle closure glaucoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Conjunctival haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Dry eye	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Eye haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Eye pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Eye swelling	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Eye ulcer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Glaucoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Lacrimation increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Metamorphopsia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Photophobia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Ocular discomfort	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Photopsia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Ocular hyperaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Periorbital swelling	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Retinal detachment	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Retinal haemorrhage	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Scleral hyperaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Trichiasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Vision blurred	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Visual impairment	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Vitreous detachment	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Asthenia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Eye disorders Vitreous floaters	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Chills	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal discomfort	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal distension	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal hernia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal pain	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	9.8% 9/92 • Number of events 9 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	9.2% 8/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Anal incontinence	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Bowel movement irregularity	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Cheilitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Colitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Constipation	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	25.0% 23/92 • Number of events 26 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	28.6% 4/14 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	25.3% 22/87 • Number of events 25 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Crohn's disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Defaecation urgency	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Diarrhoea	80.0% 4/5 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	37.0% 34/92 • Number of events 61 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	46.2% 6/13 • Number of events 10 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	42.9% 6/14 • Number of events 10 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	34.5% 30/87 • Number of events 54 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Dry mouth	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Dyspepsia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.0% 12/92 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Dysphagia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Eructation	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Faeces soft	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Flatulence	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Food poisoning	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Gastritis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Gingival bleeding	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Haematochezia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Haemorrhoids	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Hiatus hernia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Intestinal mass	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Large intestine polyp	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Lip erythema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Mouth ulceration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Nausea	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	22.8% 21/92 • Number of events 29 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	30.8% 4/13 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	35.7% 5/14 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.8% 19/87 • Number of events 26 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Noninfective gingivitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Oesophagitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Oral blood blister	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Oral pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Retching	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Stomatitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Tongue ulceration	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Toothache	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	17.4% 16/92 • Number of events 21 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	18.4% 16/87 • Number of events 21 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Chest discomfort	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Chest pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Cyst	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Crepitations	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Fatigue	20.0% 1/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	31.5% 29/92 • Number of events 41 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	32.2% 28/87 • Number of events 39 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Feeling cold	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Fibrosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Gait disturbance	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Hernia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders General physical health deterioration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Gravitational oedema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Influenza like illness	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Malaise	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Mucosal inflammation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Non-cardiac chest pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Oedema peripheral	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.0% 11/92 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Peripheral swelling	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Physical deconditioning	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Pyrexia	20.0% 1/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.3% 15/92 • Number of events 24 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.1% 14/87 • Number of events 22 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Swelling	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Ulcer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Ulcer haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Vaccination site rash	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Vessel puncture site bruise	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Vessel puncture site haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
General disorders Vessel puncture site pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Hepatobiliary disorders Biliary colic	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Hepatobiliary disorders Cholelithiasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Immune system disorders Allergic reaction to excipient	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Immune system disorders Allergy to arthropod bite	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Immune system disorders Hypogammaglobulinaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Immune system disorders Seasonal allergy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Bronchitis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.7% 8/92 • Number of events 13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 12 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Covid-19	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Candida infection	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Cellulitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Clostridium difficile colitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Conjunctivitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Cystitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Diverticulitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Ear infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Epididymitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Epiglottitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Erysipelas	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Escherichia urinary tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Eye infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Eyelid infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Fungal infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Fungal skin infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Gastroenteritis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Gastroenteritis norovirus	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Gastroenteritis viral	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Herpes simplex	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Herpes virus infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Herpes zoster	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Hordeolum	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Influenza	20.0% 1/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 9 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Labyrinthitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Laryngitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Localised infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Lower respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	20.7% 19/92 • Number of events 34 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.8% 19/87 • Number of events 34 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Nasopharyngitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.0% 11/92 • Number of events 12 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 12 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Onychomycosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Oral candidiasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Oral herpes	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Otitis externa	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Otitis media	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Paronychia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pharyngitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pharyngitis streptococcal	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pneumococcal infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pneumonia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Pneumonia bacterial	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Post procedural cellulitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.0% 12/92 • Number of events 21 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.8% 12/87 • Number of events 21 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Respiratory tract infection viral	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Rhinitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.9% 10/92 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	11.5% 10/87 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Rhinovirus infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Septic shock	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Sinusitis	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.0% 12/92 • Number of events 20 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	11.5% 10/87 • Number of events 17 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Skin infection	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Soft tissue infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Subcutaneous abscess	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Superinfection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Tinea infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Tooth abscess	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Tooth infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Upper respiratory tract infection	60.0% 3/5 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	29.3% 27/92 • Number of events 44 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	28.6% 4/14 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	27.6% 24/87 • Number of events 38 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Urinary tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.0% 12/92 • Number of events 34 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.8% 12/87 • Number of events 34 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Urosepsis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Vaginal infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Viral infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Infections and infestations Wound infection	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Animal bite	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Back injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Compression fracture	0.00% 0/4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Contusion	60.0% 3/5 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	29.3% 27/92 • Number of events 42 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	27.6% 24/87 • Number of events 36 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Eye contusion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Fall	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	9.8% 9/92 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Fractured sacrum	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Incision site haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Joint injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Limb injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Oral contusion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Periorbital haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Post procedural contusion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Road traffic accident	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Injury, poisoning and procedural complications Wound	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Alanine aminotransferase increased	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Aspartate aminotransferase increased	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood bilirubin unconjugated increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood calcium decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood creatinine increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood folate decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood immunoglobulin g decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Blood urine present	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Cardiac murmur	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Prostatic specific antigen increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Respiratory syncytial virus test positive	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Serum ferritin decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Vitamin d decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Weight decreased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Flushing	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Investigations Weight increased	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Decreased appetite	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.3% 15/92 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.1% 14/87 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Folate deficiency	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Gout	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Iron deficiency	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Polydipsia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Vitamin b12 deficiency	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Metabolism and nutrition disorders Vitamin d deficiency	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Arthralgia	60.0% 3/5 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	31.5% 29/92 • Number of events 43 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	38.5% 5/13 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	35.7% 5/14 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	29.9% 26/87 • Number of events 38 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Arthritis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Axillary mass	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	22.8% 21/92 • Number of events 28 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	24.1% 21/87 • Number of events 28 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Bursitis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Jaw clicking	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Muscle mass	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Myalgia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.7% 8/92 • Number of events 21 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 20 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.3% 15/92 • Number of events 19 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	17.2% 15/87 • Number of events 19 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Pain in jaw	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Spondylitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Musculoskeletal and connective tissue disorders Trigger finger	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Phyllodes tumour	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Amnesia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Balance disorder	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Cerebrovascular accident	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Dementia alzheimer's type	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Dizziness	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.9% 22/92 • Number of events 26 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	38.5% 5/13 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	35.7% 5/14 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.0% 20/87 • Number of events 24 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Dizziness postural	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Dysgeusia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Essential tremor	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Head discomfort	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Headache	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	42.4% 39/92 • Number of events 52 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	38.5% 5/13 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	35.7% 5/14 • Number of events 9 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	42.5% 37/87 • Number of events 49 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Hypoaesthesia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Hypogeusia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Intracranial mass	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Lethargy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Memory impairment	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Mental impairment	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Migraine	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Muscle contractions involuntary	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Neuralgia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Neuropathy peripheral	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Paraesthesia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.9% 10/92 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	11.5% 10/87 • Number of events 11 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Parosmia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Phrenic nerve paralysis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Presyncope	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Restless legs syndrome	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Sciatica	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Sedation	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Sensory disturbance	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Syncope	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Taste disorder	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Transient ischaemic attack	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Nervous system disorders Tremor	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Abnormal dreams	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Anxiety	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Claustrophobia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Confusional state	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Depressed mood	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Depression	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Hallucination	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Insomnia	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	30.8% 4/13 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	28.6% 4/14 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Irritability	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Poor quality sleep	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Procedural anxiety	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Psychiatric disorders Restlessness	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Chromaturia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Dysuria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Haematuria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.3% 4/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Micturition urgency	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Nephrolithiasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Nocturia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Pollakiuria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Polyuria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Proteinuria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Renal injury	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Urinary incontinence	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Urinary tract pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Renal and urinary disorders Urine abnormality	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Abnormal uterine bleeding	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Breast pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Dyspareunia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Ejaculation disorder	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Endometrial thickening	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Haematospermia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Pelvic pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Prostatitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Testicular pain	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Testicular swelling	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Vaginal discharge	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Reproductive system and breast disorders Vulvovaginal pain	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Allergic respiratory symptom	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Cough	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	26.1% 24/92 • Number of events 32 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	25.3% 22/87 • Number of events 29 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.2% 14/92 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	23.1% 3/13 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.1% 14/87 • Number of events 15 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.0% 12/92 • Number of events 16 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/12 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	12.6% 11/87 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Lung opacity	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Nasal oedema	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Productive cough	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	10.9% 10/92 • Number of events 12 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	9.2% 8/87 • Number of events 10 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Respiratory symptom	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Sputum retention	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Blister	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Capillaritis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Dermatitis bullous	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.0% 7/87 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Ecchymosis	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	4.6% 4/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Erythema	40.0% 2/5 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	8.7% 8/92 • Number of events 10 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 8 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Hyperhidrosis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Ingrown hair	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Macule	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Nail dystrophy	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.4% 5/92 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	100.0% 1/1 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	21.4% 3/14 • Number of events 4 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Pigmentation disorder	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Pruritus	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.1% 13/92 • Number of events 14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	13.8% 12/87 • Number of events 13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Rash	40.0% 2/5 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	18.5% 17/92 • Number of events 20 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	17.2% 15/87 • Number of events 17 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.4% 3/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Scab	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin induration	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	16.3% 15/92 • Number of events 19 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	15.4% 2/13 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	14.3% 2/14 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	17.2% 15/87 • Number of events 19 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Social circumstances Walking disability	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Surgical and medical procedures Tooth extraction	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Aortic dilatation	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/92 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/87 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Deep vein thrombosis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Essential hypertension	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Haematoma	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.6% 7/92 • Number of events 7 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Haemorrhage	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Hot flush	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Hypertension	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	5.7% 5/87 • Number of events 5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Hypotension	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Lymphoedema	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.2% 2/92 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Orthostatic hypotension	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.5% 6/92 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.7% 1/13 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	7.1% 1/14 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	6.9% 6/87 • Number of events 6 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Pallor	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Peripheral venous disease	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Phlebitis	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Varicose vein	0.00% 0/5 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/92 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	1.1% 1/87 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.
Vascular disorders Vasculitis	20.0% 1/5 • Number of events 1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	3.3% 3/92 • Number of events 3 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/13 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/1 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	0.00% 0/14 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.	2.3% 2/87 • Number of events 2 • Reported Adverse Events (AEs) include events from the first dose of study drug until 30 days after the last dose of the study drug or start of a new anti-cancer therapy (whichever came first), assessed up to approximately 6 years and 7 months. In original protocol, subjects were planned to be randomized 1:1 into 2 cohorts: Acala 100 mg BIDx28 days and 200 mg QDx28 days respectively. After enrollment started, 6 pts received Acala 200 mg QD (5 pts previously treated,1 pt treatment naïve).Per safety and occupancy data in CLL pts, a protocol amendment was made on 13MAR2015, and the 6 pts on 200 mg QD were switched to 100 BID for the remainder of the study. Median 200 mg QD exposure prior to switch was 6.9 \[range: 2.4-13.8\] months.

Additional Information

Global Clinical Lead

Acerta Pharma

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER