Trial Outcomes & Findings for A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma (NCT NCT00290706)

Last Updated: 2019-05-28

Results Overview

Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission \[CR\] and Partial Remission \[PR\]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where: CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=\> 50% decrease in SPD of the six largest dominant nodes or nodal masses

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

32 participants

Primary outcome timeframe

At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8

Results posted on

2019-05-28

Participant Flow

The study opened for accrual to phase I on September 26, 2005 with first patient treated April 7 2006.The study was closed on October 17 2007 to phase I and opened to phase II on December 18 2007. The study closed permanently March 9 2011 with a total accrual of 32 patients treated on the study before reaching the total accrual goal.

Participant milestones

Participant milestones
Measure	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Overall Study STARTED	5	6	7	14
Overall Study Attempted1st Cycle	5	6	7	14
Overall Study Reached 1st Response/Cycle 3	0	0	1	2
Overall Study COMPLETED	0	0	1	2
Overall Study NOT COMPLETED	5	6	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Overall Study Withdrawal by Subject	2	0	0	0
Overall Study Progressive Disease	3	5	4	10
Overall Study Adverse Event	0	1	2	0
Overall Study Receive auto transplant or radiation	0	0	0	1
Overall Study Physician Decision	0	0	0	1

Baseline Characteristics

A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2 n=5 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 n=6 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8 n=7 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15 n=14 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants	22 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	14 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants	29 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants	25 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	5 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants	32 Participants n=21 Participants

PRIMARY outcome

Timeframe: At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8

Population: Patients must complete 3 cycles of treatment to be evaluable for this outcome measure. Only 3 patients reached Cycle 3 and the study closed before accrual was met due to lack of efficacy. Below shows response of patients that reached Cycle 3 and is not a reflection of response rate.

Outcome measures

Outcome measures
Measure	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8 n=1 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15 n=2 Participants Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment.	—	—	1 participants	2 participants

SECONDARY outcome

Timeframe: At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

Population: Study was terminated due to lack of efficacy. Data not collected for analysis of outcome measure.

Time to treatment failure and duration of response will be measured by CT Scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

Population: The study was terminated early due to lack of efficacy. Data not collect for analysis of this outcome measure.

Overall survival will be evaluated every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment

Population: The study was terminated before total accrual was met due to lack of efficacy. Data was not collected for analysis for this outcome measure

Safety and tolerability of the study drugs will be assessed on Day 1 and on either Day 8 or Day 15 of each treatment cycle (1 Cycle - 28 days) while on active treatment; and 30 days post last treatment. Adverse Events that are experienced by patients, determined to be either grade 3 or grade 4 and at least possibly related to at least one of the study drugs as assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) will be collected. In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2

Serious events: 4 serious events

Other events: 5 other events

Deaths: 5 deaths

Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2

Serious events: 2 serious events

Other events: 6 other events

Deaths: 6 deaths

Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8

Serious events: 3 serious events

Other events: 7 other events

Deaths: 7 deaths

Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15

Serious events: 6 serious events

Other events: 14 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Leo Gordon

Northwestern University

Phone: 312-695-4520

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2 n=5 participants at risk Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 n=6 participants at risk Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8 n=7 participants at risk Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15 n=14 participants at risk Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Renal and urinary disorders Renal Failure	20.0% 1/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
General disorders Multi organ failure - death	20.0% 1/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive disease - death	40.0% 2/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	14.3% 1/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	14.3% 2/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
General disorders Fever	20.0% 1/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	7.1% 1/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Pneumonia leading to death	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	16.7% 1/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Nervous system disorders Headache	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	16.7% 1/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Cardiac disorders Hypertension	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	16.7% 1/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Infection NOS	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	16.7% 1/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Pneumonia	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	16.7% 1/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Sepsis	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	14.3% 1/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Bacteremia	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	14.3% 1/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	14.3% 1/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	7.1% 1/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	7.1% 1/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Renal and urinary disorders Rectal bleeding	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	7.1% 1/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Infections and infestations Neutropenia	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	7.1% 1/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Blood and lymphatic system disorders Anemia	0.00% 0/5 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	33.3% 2/6 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/7 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.	0.00% 0/14 • Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.