Trial Outcomes & Findings for Rollover Study of BMS-354825 in Patients With CML and Ph+ALL (NCT NCT01030718)
NCT ID: NCT01030718
Last Updated: 2010-12-14
Results Overview
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
54 participants
Primary outcome timeframe
baseline; every 4 weeks (if on study < 6 months, including CA180-031(NCT00337454); every 12 weeks (if on study >=6 months and <=2 years); every 24 weeks (if on study >2 years); at discontinuation
Results posted on
2010-12-14
Participant Flow
CA180-031 = NCT00337454; CA180-036 = NCT01030718
55 participants were randomized to study CA180-031; 1 participant with chronic myelogenous leukemia-chronic phase (CML-CP) was withdrawn prior to dosing due to thrombocytopenia. 54 subjects were treated; 44 subjects finished the study period of CA180-031 and transferred CA180-036. Analyses were done on the population enrolled into CA180-031 study.
Participant milestones
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Philadelphia chromosome positive (Ph+) ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Studies CA180-031 and -036 Combined
STARTED
|
30
|
11
|
13
|
|
Studies CA180-031 and -036 Combined
COMPLETED
|
26
|
2
|
1
|
|
Studies CA180-031 and -036 Combined
NOT COMPLETED
|
4
|
9
|
12
|
|
Study CA180-036 Only
STARTED
|
29
|
9
|
6
|
|
Study CA180-036 Only
COMPLETED
|
26
|
2
|
1
|
|
Study CA180-036 Only
NOT COMPLETED
|
3
|
7
|
5
|
Reasons for withdrawal
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Philadelphia chromosome positive (Ph+) ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Studies CA180-031 and -036 Combined
Insufficient effect
|
1
|
1
|
11
|
|
Studies CA180-031 and -036 Combined
Adverse Event
|
3
|
5
|
1
|
|
Studies CA180-031 and -036 Combined
Death
|
0
|
1
|
0
|
|
Studies CA180-031 and -036 Combined
other reasons
|
0
|
2
|
0
|
|
Study CA180-036 Only
insufficient effect
|
1
|
1
|
5
|
|
Study CA180-036 Only
Adverse Event
|
2
|
3
|
0
|
|
Study CA180-036 Only
Death
|
0
|
1
|
0
|
|
Study CA180-036 Only
Other Reasons
|
0
|
2
|
0
|
Baseline Characteristics
Rollover Study of BMS-354825 in Patients With CML and Ph+ALL
Baseline characteristics by cohort
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=11 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=13 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<65 years
|
26 participants
n=5 Participants
|
8 participants
n=7 Participants
|
10 participants
n=5 Participants
|
44 participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
10 participants
n=4 Participants
|
|
Age Continuous
|
51.5 years
n=5 Participants
|
57.0 years
n=7 Participants
|
64.0 years
n=5 Participants
|
55.5 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
30 participants
n=5 Participants
|
11 participants
n=7 Participants
|
13 participants
n=5 Participants
|
54 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 0
|
27 participants
n=5 Participants
|
6 participants
n=7 Participants
|
9 participants
n=5 Participants
|
42 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 1
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
4 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 2
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 3
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 4
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Eastern Oncology Cooperative Group Performance Status
Status = 5
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Imatinib Status
Resistant
|
18 participants
n=5 Participants
|
8 participants
n=7 Participants
|
9 participants
n=5 Participants
|
35 participants
n=4 Participants
|
|
Imatinib Status
Intolerant
|
12 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
19 participants
n=4 Participants
|
|
Body Weight
|
64.05 kg
n=5 Participants
|
58.00 kg
n=7 Participants
|
53.20 kg
n=5 Participants
|
60.55 kg
n=4 Participants
|
|
Height
|
163.65 cm
n=5 Participants
|
161.00 cm
n=7 Participants
|
164.50 cm
n=5 Participants
|
163.25 cm
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline; every 4 weeks (if on study < 6 months, including CA180-031(NCT00337454); every 12 weeks (if on study >=6 months and <=2 years); every 24 weeks (if on study >2 years); at discontinuationPopulation: All treated participants. Number of deaths represents all reported deaths, including after the study end. For AEs leading to discontinuation: 4 in CML-CP=1 insufficient effect (IE) +3 AEs in Participant Flow (PF); 7 in CML-AP/BP= 1 death + 5 AEs + 1 IE in PF; 4 in Ph+ALL=3 IE + 1AE in PF.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=11 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=13 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation
AEs (symptoms/signs and laboratory abnormalities)
|
30 participants
|
11 participants
|
13 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation
SAEs (symptoms/signs and laboratory abnormalities)
|
13 participants
|
9 participants
|
11 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation
Deaths
|
1 participants
|
2 participants
|
3 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation
AEs that led to discontinuation
|
4 participants
|
7 participants
|
4 participants
|
SECONDARY outcome
Timeframe: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)Population: Treated CML-CP participants
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Philadelphia positive \[Ph+\] Cells in Metaphase in BM).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=11 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=12 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response
Major cytogenetic response (MCyR)
|
77 Percentage of Participants
Interval 57.7 to 90.1
|
61 Percentage of Participants
Interval 35.7 to 82.7
|
100 Percentage of Participants
Interval 73.5 to 100.0
|
|
Participants With Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response
Complete cytogenetic response (CCyR)
|
63 Percentage of Participants
Interval 43.9 to 80.1
|
44 Percentage of Participants
Interval 21.5 to 69.2
|
92 Percentage of Participants
Interval 61.5 to 99.8
|
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Treated CML-AP/BP participants
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=11 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=8 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=3 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response
Major cytogenetic response (MCyR)
|
27 Percentage of Participants
Interval 6.0 to 61.0
|
38 Percentage of Participants
Interval 8.5 to 75.5
|
0 Percentage of Participants
Interval 0.0 to 0.0
|
|
Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response
Complete cytogenetic response (CCyR)
|
18 Percentage of Participants
Interval 2.3 to 51.8
|
25 Percentage of Participants
Interval 3.2 to 65.1
|
0 Percentage of Participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Treated Ph+ ALL participants
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=13 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=9 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=4 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL): Percentage of Participants With Cytogenetic Response
Major cytogenetic response (MCyR)
|
54 Percentage of Participants
Interval 25.1 to 80.8
|
33 Percentage of Participants
Interval 7.5 to 70.1
|
100 Percentage of Participants
Interval 39.8 to 100.0
|
|
Participants With Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL): Percentage of Participants With Cytogenetic Response
Complete cytogenetic response (CCyR)
|
46 Percentage of Participants
Interval 19.2 to 74.9
|
22 Percentage of Participants
Interval 2.8 to 60.0
|
100 Percentage of Participants
Interval 39.8 to 100.0
|
SECONDARY outcome
Timeframe: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454),Population: Participants achieving CCyR
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=19 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-CP: Time to Complete Cytogenetic Response (CCyR)
|
169 Days
Interval 83.0 to 841.0
|
—
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Participants achieving CCyR
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=2 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=6 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-AP/BP and Ph+ ALL: Time to Complete Cytogenetic Response (CCyR)
|
215 Days
Interval 93.0 to 337.0
|
82 Days
Interval 9.0 to 89.0
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)Population: Participants achieving CCyR. Median duration of CCyR was not yet reached in the CML-CP group.
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of progressed disease (PD) or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Participants achieving CCyR. Median duration of CCyR was not yet reached in the CML-AP/BP group.
Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of PD or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=6 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-AP/BP and Ph+ALL: Duration of Complete Cytogenetic Response (CCyR)
|
—
|
96.5 Days
Interval 35.0 to 705.0
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)Population: Time to MCyR was computed only for participants whose best response was CCyR or PCyR.
Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=23 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-CP: Time to Major Cytogenetic Response (MCyR)
|
169 Days
Interval 83.0 to 1006.0
|
—
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Time to MCyR was computed only for participants whose best response was CCyR or PCyR.
Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=3 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=7 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-AP/BP and Ph+ALL: Time to Major Cytogenetic Response (MCyR)
|
85 Days
Interval 84.0 to 93.0
|
85 Days
Interval 5.0 to 96.0
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)Population: Duration of MCyR was computed for subjects whose best response was either CCyR or PCyR. Median duration of MCyR was not yet reached in the CML-CP arm.
Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafterPopulation: Duration of MCyR was computed for subjects whose best response was either CCyR or PCyR. Median duration of MCyR was not yet reached in the CML-AP/BP arm.
Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=7 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-AP/BP and Ph+ ALL: Duration of Major Cytogenetic Response (MCyR)
|
—
|
85 Days
Interval 35.0 to 705.0
|
—
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454), every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Treated CML-CP participants
CHR=all of the following criteria: white blood cell count (WBC) ≤institutional upper limit of normal(ULN); platelets \<450,000/mm³; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils \<20%; no extramedullary involvement.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=18 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=12 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-CP: Percentage of Participants With Complete Hematologic Response (CHR)
|
93 Percentage of Participants
Interval 77.9 to 99.2
|
89 Percentage of Participants
Interval 65.3 to 98.6
|
100 Percentage of Participants
Interval 73.5 to 100.0
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Treated CML-AP/BP participants
Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=WBC \<ULN; absolute neutrophil count (ANC) \>1,000/mm3; platelets \>100,000/mm3; no blasts or promyelocytes in peripheral blood; BM blasts ≤5%; \<5% myelocytes + metamyelocytes in peripheral blood; \<20% basophils in peripheral blood; no extramedullary involvement. NEL=(see Outcome Measure 15, below). Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=11 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=8 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=3 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With CML-AP/BP: Percentage of Participants With Hematologic Response
Overall hematologic response (OHR)
|
73 Percentage of Participants
Interval 39.0 to 94.0
|
75 Percentage of Participants
Interval 34.9 to 96.8
|
67 Percentage of Participants
Interval 9.4 to 99.2
|
|
Participants With CML-AP/BP: Percentage of Participants With Hematologic Response
Major hematologic response (MaHR)
|
73 Percentage of Participants
Interval 39.0 to 94.0
|
75 Percentage of Participants
Interval 34.9 to 96.8
|
67 Percentage of Participants
Interval 9.4 to 99.2
|
|
Participants With CML-AP/BP: Percentage of Participants With Hematologic Response
Complete hematologic response (CHR)
|
55 Percentage of Participants
Interval 23.4 to 83.3
|
75 Percentage of Participants
Interval 34.9 to 96.8
|
0 Percentage of Participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Treated Ph+ ALL participants
Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=(see Outcome Measure 14, above). NEL=WBC ≤ULN; BM blasts ≤5%; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; \<20% peripheral blood basophils; no extramedullary involvement; and at least 1 of the following: ANC ≥500/mm3 and \<2000/mm3 or platelets ≥20,000/mm3 and \<100,000/mm3. Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=13 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=9 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=4 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With Ph+ ALL: Percentage of Participants With Hematologic Response
Overall hematologic response (OHR)
|
69 Percentage of Participants
Interval 38.6 to 90.9
|
56 Percentage of Participants
Interval 21.2 to 86.3
|
100 Percentage of Participants
Interval 39.8 to 100.0
|
|
Participants With Ph+ ALL: Percentage of Participants With Hematologic Response
Major hematologic response (MaHR)
|
46 Percentage of Participants
Interval 19.2 to 74.9
|
33 Percentage of Participants
Interval 7.5 to 70.1
|
75.5 Percentage of Participants
Interval 19.4 to 99.4
|
|
Participants With Ph+ ALL: Percentage of Participants With Hematologic Response
Complete hematologic response (CHR)
|
15 Percentage of Participants
Interval 1.9 to 45.4
|
0 Percentage of Participants
Interval 0.0 to 0.0
|
50 Percentage of Participants
Interval 6.8 to 93.2
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Participants achieving CHR
CHR=all of the following criteria: WBC ≤institutional upper limit of normal(ULN); platelets \<450,000/mm³; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils \<20%; no extramedullary involvement. Time to CHR=time from first dose of dasatinib until the first day criteria for CHR are met provided they are confirmed 28 days later and was computed only for chronic phase CML subjects whose best response is CHR. Subjects who neither progressed nor died were censored at date of last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=29 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=6 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=2 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Time to Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL
|
12.5 Days
Interval 3.0 to 343.0
|
89 Days
Interval 57.0 to 307.0
|
98.5 Days
Interval 57.0 to 140.0
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Participants achieving CHR. Duration of CHR in the CML AP/BP arm has not yet been reached.
Duration of CHR was computed only for chronic phase CML subjects whose best response is CHR. It was measured from the first day complete hematologic response criteria are met provided they are confirmed 28 days later until the date treatment is discontinued due to PD or death. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=29 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=2 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Duration of Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL
|
1160 Days
Interval 153.0 to 1310.0
|
—
|
373 Days
Interval 102.0 to 644.0
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Participants achieving MaHR
Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Time to major hematologic response (MaHR)=time from first dose of dasatinib until the first day the measurement criteria for MaHR and is computed only for advanced diseases subjects whose best response is a major hematologic response. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=8 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=6 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Time to Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL
|
45.5 Days
Interval 8.0 to 102.0
|
59 Days
Interval 9.0 to 151.0
|
—
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Duration of MaHR was computed only for advanced diseases subjects whose best response is a MaHR and was measured from the first day MaHR criteria are met, provided they were confirmed 28 days later until the date of PD or death. Median Duration of MaHR was not yet reached in the CML-AP/BP arm.
Major Hematologic Response (MaHR)=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=6 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Duration of Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL
|
—
|
102.5 Days
Interval 35.0 to 774.0
|
—
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: OHR was computed only for subjects whose best response is CHR or MaHR or Minor HR (MiHR).
The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Time to OHR = time from first dose of dasatinib until the first day measurement criteria are first met for hematologic response provided they were confirmed 28 days later. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=8 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=9 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Time to Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL
|
38.5 Days
Interval 8.0 to 68.0
|
13 Days
Interval 2.0 to 68.0
|
—
|
SECONDARY outcome
Timeframe: baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuationPopulation: Duration of OHR was computed only for participants whose best response was CHR or a MaHR or MiHR \& was measured from the first day hematologic response criteria were met, provided they were confirmed 28 days later until the date of PD or death. Median duration of OHR in the CML-AP/BP arm was not yet reached.
The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=9 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Duration of Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL
|
—
|
104 Days
Interval 30.0 to 774.0
|
—
|
SECONDARY outcome
Timeframe: At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter, and at discontinuationPopulation: Treated participants
Detectable BCR-ABL transcripts (b3a2, b2a2 or minor) \>=2.0 log copy/micrograms RNA, as measured by real-time quantitative PCR (RQ-PCR) at baseline and best achievement post-dose.
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=11 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=13 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Participants With Detectable Mutations of RNA (mRNA) of BCR-ABL at Baseline and at Best Achievement
Baseline
|
28 participants
|
11 participants
|
10 participants
|
|
Participants With Detectable Mutations of RNA (mRNA) of BCR-ABL at Baseline and at Best Achievement
Best Achievement
|
12 participants
|
7 participants
|
6 participants
|
SECONDARY outcome
Timeframe: At baseline and discontinuation--the study period was extended until the launch of dasatinib in Japan, January 2009.Population: Treated participants
Point mutations of BCR-ABL detected or undetected in the Quantitative real-time PCR polymerase chain reaction (RQ-PCR) products
Outcome measures
| Measure |
CML - Chronic Phase (CML-CP)
n=30 Participants
Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
CML - Accelerated Phase and Blast Phase (CML-AP/BP)
n=11 Participants
Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
n=13 Participants
Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|---|---|
|
Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS)
Undetectable at BL → Detectable at EOS
|
1 participants
|
1 participants
|
7 participants
|
|
Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS)
Detectable at BL → Detectable at EOS
|
2 participants
|
1 participants
|
3 participants
|
|
Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS)
Detectable at BL → Undetectable at EOS
|
2 participants
|
0 participants
|
0 participants
|
|
Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS)
Detectable at BL → Not Analyzed at EOS
|
1 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: At any visit of later than Day 7, draw sample(s) at pretreatment trough (within 1 hour prior to dosing) or between 3 hours following treatment and prior to the next dosePopulation: There was no individual PK analysis done for this study; analyses were integrated and evaluated as a part of population PK of this drug.
Blood samples for pharmacokinetic analysis of Dasatinib BID that will contribute to population pharmacokinetic modeling were collected.
Outcome measures
Outcome data not reported
Adverse Events
All Treated Participants
Serious events: 33 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Treated Participants
n=54 participants at risk
Imatinib resistant or intolerant CML-CP disease cohort, Imatinib resistant or intolerant CML-AP/BP disease cohort, and Ph+ ALL subjects with resistance or intolerance to past therapy. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.7%
2/54
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.7%
2/54
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
1.9%
1/54
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.9%
1/54
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.9%
1/54
|
|
Cardiac disorders
Atrial tachycardia
|
1.9%
1/54
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.9%
1/54
|
|
Gastrointestinal disorders
Anal fistula
|
1.9%
1/54
|
|
Gastrointestinal disorders
Enterocolitis
|
1.9%
1/54
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.9%
1/54
|
|
Gastrointestinal disorders
Haematochezia
|
1.9%
1/54
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.9%
1/54
|
|
Gastrointestinal disorders
Ileus
|
1.9%
1/54
|
|
Gastrointestinal disorders
Periodontitis
|
1.9%
1/54
|
|
General disorders
Pyrexia
|
5.6%
3/54
|
|
General disorders
Malaise
|
1.9%
1/54
|
|
General disorders
Therapeutic response decreased
|
1.9%
1/54
|
|
General disorders
Disease progression
|
1.9%
1/54
|
|
Infections and infestations
Pneumonia
|
11.1%
6/54
|
|
Infections and infestations
Enteritis infectious
|
3.7%
2/54
|
|
Infections and infestations
Cellulitis
|
1.9%
1/54
|
|
Infections and infestations
Gastroenteritis
|
1.9%
1/54
|
|
Infections and infestations
Perianal abscess
|
1.9%
1/54
|
|
Infections and infestations
Pseudomembranous colitis
|
1.9%
1/54
|
|
Infections and infestations
Enterocolitis infectious
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
3.7%
2/54
|
|
Injury, poisoning and procedural complications
Brain herniation
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Fracture
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Haemothorax
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Overdose
|
1.9%
1/54
|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
1/54
|
|
Investigations
Platelet count decreased
|
7.4%
4/54
|
|
Investigations
Haemoglobin decreased
|
3.7%
2/54
|
|
Investigations
Alanine aminotransferase increased
|
1.9%
1/54
|
|
Investigations
Aspartate aminotransferase increased
|
1.9%
1/54
|
|
Investigations
Haematocrit decreased
|
1.9%
1/54
|
|
Investigations
Neutrophil count decreased
|
1.9%
1/54
|
|
Investigations
Red blood cell count decreased
|
1.9%
1/54
|
|
Investigations
White blood cell count decreased
|
1.9%
1/54
|
|
Metabolism and nutrition disorders
Anorexia
|
1.9%
1/54
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
1.9%
1/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent
|
11.1%
6/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome
|
3.7%
2/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
1.9%
1/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
1.9%
1/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast cell crisis
|
1.9%
1/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
1.9%
1/54
|
|
Nervous system disorders
Cerebral haemorrhage
|
5.6%
3/54
|
|
Nervous system disorders
Convulsion
|
1.9%
1/54
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
1.9%
1/54
|
|
Nervous system disorders
Brain mass
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.6%
3/54
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
1.9%
1/54
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
1.9%
1/54
|
|
Vascular disorders
Haematoma
|
1.9%
1/54
|
Other adverse events
| Measure |
All Treated Participants
n=54 participants at risk
Imatinib resistant or intolerant CML-CP disease cohort, Imatinib resistant or intolerant CML-AP/BP disease cohort, and Ph+ ALL subjects with resistance or intolerance to past therapy. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
42.6%
23/54
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
11.1%
6/54
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.4%
4/54
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
3/54
|
|
Cardiac disorders
Cardiomegaly
|
9.3%
5/54
|
|
Cardiac disorders
Palpitations
|
9.3%
5/54
|
|
Cardiac disorders
Pericardial effusion
|
7.4%
4/54
|
|
Cardiac disorders
Sinus bradycardia
|
5.6%
3/54
|
|
Endocrine disorders
Hypothyroidism
|
5.6%
3/54
|
|
Eye disorders
Eyelid oedema
|
18.5%
10/54
|
|
Eye disorders
Conjunctival haemorrhage
|
14.8%
8/54
|
|
Eye disorders
Conjunctival hyperaemia
|
9.3%
5/54
|
|
Eye disorders
Vision blurred
|
7.4%
4/54
|
|
Eye disorders
Conjunctivitis
|
5.6%
3/54
|
|
Gastrointestinal disorders
Diarrhoea
|
59.3%
32/54
|
|
Gastrointestinal disorders
Nausea
|
38.9%
21/54
|
|
Gastrointestinal disorders
Constipation
|
33.3%
18/54
|
|
Gastrointestinal disorders
Vomiting
|
29.6%
16/54
|
|
Gastrointestinal disorders
Stomatitis
|
27.8%
15/54
|
|
Gastrointestinal disorders
Abdominal pain
|
13.0%
7/54
|
|
Gastrointestinal disorders
Toothache
|
13.0%
7/54
|
|
Gastrointestinal disorders
Abdominal distension
|
11.1%
6/54
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.1%
6/54
|
|
Gastrointestinal disorders
Cheilitis
|
9.3%
5/54
|
|
Gastrointestinal disorders
Gingivitis
|
9.3%
5/54
|
|
Gastrointestinal disorders
Haematochezia
|
9.3%
5/54
|
|
Gastrointestinal disorders
Abdominal pain lower
|
7.4%
4/54
|
|
Gastrointestinal disorders
Gingival bleeding
|
7.4%
4/54
|
|
Gastrointestinal disorders
Haemorrhoids
|
7.4%
4/54
|
|
Gastrointestinal disorders
Stomach discomfort
|
7.4%
4/54
|
|
Gastrointestinal disorders
Dental caries
|
5.6%
3/54
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
5.6%
3/54
|
|
Gastrointestinal disorders
Gingival swelling
|
5.6%
3/54
|
|
General disorders
Pyrexia
|
50.0%
27/54
|
|
General disorders
Malaise
|
42.6%
23/54
|
|
General disorders
Oedema
|
33.3%
18/54
|
|
General disorders
Oedema peripheral
|
16.7%
9/54
|
|
General disorders
Face oedema
|
13.0%
7/54
|
|
General disorders
Pain
|
13.0%
7/54
|
|
General disorders
Chest pain
|
9.3%
5/54
|
|
General disorders
Chills
|
9.3%
5/54
|
|
General disorders
Chest discomfort
|
5.6%
3/54
|
|
General disorders
Fatigue
|
5.6%
3/54
|
|
General disorders
Hypothermia
|
5.6%
3/54
|
|
Immune system disorders
Seasonal allergy
|
5.6%
3/54
|
|
Infections and infestations
Nasopharyngitis
|
53.7%
29/54
|
|
Infections and infestations
Folliculitis
|
14.8%
8/54
|
|
Infections and infestations
Pharyngitis
|
11.1%
6/54
|
|
Infections and infestations
Bronchitis
|
9.3%
5/54
|
|
Infections and infestations
Gastroenteritis
|
7.4%
4/54
|
|
Infections and infestations
Infection
|
7.4%
4/54
|
|
Infections and infestations
Influenza
|
5.6%
3/54
|
|
Injury, poisoning and procedural complications
Excoriation
|
13.0%
7/54
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
5.6%
3/54
|
|
Injury, poisoning and procedural complications
Wound
|
5.6%
3/54
|
|
Investigations
Neutrophil count decreased
|
85.2%
46/54
|
|
Investigations
Platelet count decreased
|
77.8%
42/54
|
|
Investigations
White blood cell count decreased
|
75.9%
41/54
|
|
Investigations
Blood lactate dehydrogenase increased
|
72.2%
39/54
|
|
Investigations
Lymphocyte count decreased
|
72.2%
39/54
|
|
Investigations
Aspartate aminotransferase increased
|
64.8%
35/54
|
|
Investigations
Alanine aminotransferase increased
|
63.0%
34/54
|
|
Investigations
Blood creatine phosphokinase increased
|
55.6%
30/54
|
|
Investigations
Gamma-glutamyltransferase increased
|
46.3%
25/54
|
|
Investigations
Haematocrit decreased
|
46.3%
25/54
|
|
Investigations
Haemoglobin decreased
|
46.3%
25/54
|
|
Investigations
Red blood cell count decreased
|
44.4%
24/54
|
|
Investigations
Blood phosphorus decreased
|
44.4%
24/54
|
|
Investigations
Blood albumin decreased
|
42.6%
23/54
|
|
Investigations
Protein urine present
|
42.6%
23/54
|
|
Investigations
White blood cell count increased
|
40.7%
22/54
|
|
Investigations
Protein total decreased
|
37.0%
20/54
|
|
Investigations
Blood alkaline phosphatase increased
|
35.2%
19/54
|
|
Investigations
Weight increased
|
33.3%
18/54
|
|
Investigations
Blood urine present
|
31.5%
17/54
|
|
Investigations
Weight decreased
|
31.5%
17/54
|
|
Investigations
Blood uric acid increased
|
29.6%
16/54
|
|
Investigations
CD4 lymphocytes decreased
|
29.6%
16/54
|
|
Investigations
Blood creatinine increased
|
22.2%
12/54
|
|
Investigations
Blood urea increased
|
18.5%
10/54
|
|
Investigations
Urinary sediment abnormal
|
18.5%
10/54
|
|
Investigations
Reticulocyte count decreased
|
16.7%
9/54
|
|
Investigations
Urobilin urine present
|
16.7%
9/54
|
|
Investigations
Blood potassium decreased
|
14.8%
8/54
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
14.8%
8/54
|
|
Investigations
Glucose urine present
|
14.8%
8/54
|
|
Investigations
Protein urine
|
14.8%
8/54
|
|
Investigations
Blood bilirubin increased
|
13.0%
7/54
|
|
Investigations
Blood magnesium increased
|
13.0%
7/54
|
|
Investigations
Blood potassium increased
|
13.0%
7/54
|
|
Investigations
C-reactive protein increased
|
13.0%
7/54
|
|
Investigations
Liver function test abnormal
|
13.0%
7/54
|
|
Investigations
Lymphocyte count increased
|
11.1%
6/54
|
|
Investigations
Neutrophil count increased
|
9.3%
5/54
|
|
Investigations
CD4 lymphocytes increased
|
9.3%
5/54
|
|
Investigations
Blood pressure increased
|
7.4%
4/54
|
|
Investigations
Blood sodium decreased
|
7.4%
4/54
|
|
Investigations
Prothrombin time prolonged
|
7.4%
4/54
|
|
Investigations
Reticulocyte count increased
|
7.4%
4/54
|
|
Investigations
Platelet count increased
|
7.4%
4/54
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.6%
3/54
|
|
Investigations
Blood chloride decreased
|
5.6%
3/54
|
|
Investigations
Eosinophil count increased
|
5.6%
3/54
|
|
Investigations
Urine ketone body present
|
5.6%
3/54
|
|
Metabolism and nutrition disorders
Anorexia
|
22.2%
12/54
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.1%
6/54
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
9.3%
5/54
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
3/54
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.6%
3/54
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.9%
14/54
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.4%
11/54
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
9/54
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
9/54
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
7.4%
4/54
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
5.6%
3/54
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.6%
3/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
5.6%
3/54
|
|
Nervous system disorders
Headache
|
48.1%
26/54
|
|
Nervous system disorders
Dizziness
|
13.0%
7/54
|
|
Nervous system disorders
Hypoaesthesia
|
11.1%
6/54
|
|
Nervous system disorders
Dysgeusia
|
9.3%
5/54
|
|
Psychiatric disorders
Insomnia
|
13.0%
7/54
|
|
Renal and urinary disorders
Haematuria
|
5.6%
3/54
|
|
Reproductive system and breast disorders
Gynaecomastia
|
7.4%
4/54
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
40.7%
22/54
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
38.9%
21/54
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
18.5%
10/54
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
14.8%
8/54
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.1%
6/54
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
9.3%
5/54
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
7.4%
4/54
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
7.4%
4/54
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
27/54
|
|
Skin and subcutaneous tissue disorders
Erythema
|
14.8%
8/54
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
14.8%
8/54
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.8%
8/54
|
|
Skin and subcutaneous tissue disorders
Purpura
|
14.8%
8/54
|
|
Skin and subcutaneous tissue disorders
Acne
|
13.0%
7/54
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
9.3%
5/54
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.4%
4/54
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
7.4%
4/54
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.6%
3/54
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
5.6%
3/54
|
|
Vascular disorders
Hypertension
|
9.3%
5/54
|
|
Vascular disorders
Hypotension
|
7.4%
4/54
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER