Trial Outcomes & Findings for A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia (NCT NCT00482703)
NCT ID: NCT00482703
Last Updated: 2010-12-17
Results Overview
Cytogenetic responses (CyR) are based on the percentage of Philadelphia-positive (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), and Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
23 participants
Primary outcome timeframe
Week 24
Results posted on
2010-12-17
Participant Flow
Participant milestones
| Measure |
Dasatinib 100 mg Once-daily (QD) Starting Dose
Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Dasatinib 50 mg Twice-daily (BID) Starting Dose
Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
12
|
|
Overall Study
COMPLETED
|
10
|
12
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Dasatinib 100 mg Once-daily (QD) Starting Dose
Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Dasatinib 50 mg Twice-daily (BID) Starting Dose
Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
|---|---|---|
|
Overall Study
Poor compliance
|
1
|
0
|
Baseline Characteristics
A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Dasatinib 100 mg Once-daily (QD) Starting Dose
n=11 Participants
Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Dasatinib 50 mg Twice-daily (BID) Starting Dose
n=12 Participants
Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
48.5 years
STANDARD_DEVIATION 14.2 • n=93 Participants
|
49.9 years
STANDARD_DEVIATION 16.0 • n=4 Participants
|
49.3 years
STANDARD_DEVIATION 14.8 • n=27 Participants
|
|
Age, Customized
<65 years
|
9 participants
n=93 Participants
|
10 participants
n=4 Participants
|
19 participants
n=27 Participants
|
|
Age, Customized
>=65 years
|
2 participants
n=93 Participants
|
2 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Region of Enrollment
Japan
|
11 participants
n=93 Participants
|
12 participants
n=4 Participants
|
23 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=0
|
11 participants
n=93 Participants
|
12 participants
n=4 Participants
|
23 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=1
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=2
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=3
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=4
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Eastern Cooperative Oncology Group Performace Status (ECOG-PS)
Status=5
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Imatinib Status
Imatinib-resistant
|
7 participants
n=93 Participants
|
7 participants
n=4 Participants
|
14 participants
n=27 Participants
|
|
Imatinib Status
Imatinib-intolerant
|
4 participants
n=93 Participants
|
5 participants
n=4 Participants
|
9 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: All treated participants
Cytogenetic responses (CyR) are based on the percentage of Philadelphia-positive (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), and Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=7 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
n=4 Participants
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
n=12 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
n=7 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
n=5 Participants
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
MCyR
|
45 percentage of participants
Interval 16.7 to 76.6
|
29 percentage of participants
Interval 3.7 to 71.0
|
75 percentage of participants
Interval 19.4 to 99.4
|
92 percentage of participants
Interval 61.5 to 99.8
|
86 percentage of participants
Interval 42.1 to 99.6
|
100 percentage of participants
Interval 47.8 to 100.0
|
|
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
CCyR
|
27 percentage of participants
Interval 6.0 to 61.0
|
14 percentage of participants
Interval 0.4 to 57.9
|
50 percentage of participants
Interval 6.8 to 93.2
|
58 percentage of participants
Interval 27.7 to 84.8
|
43 percentage of participants
Interval 9.9 to 81.6
|
80 percentage of participants
Interval 28.4 to 99.5
|
SECONDARY outcome
Timeframe: Throughout study period to last observation. Dosing period=6 months; if beneficial, medication may continue in the extension period (ending in January 2009). Last observation=30 days past last dosing day or the discontinuation day.Population: All treated participants
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 the development of drug dependency or drug abuse, is an important medical event.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=12 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
AEs (symptoms/signs and laboratory abnormalities)
|
11 participants
|
12 participants
|
—
|
—
|
—
|
—
|
|
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
SAEs (symptoms/signs and laboratory abnormalities)
|
4 participants
|
6 participants
|
—
|
—
|
—
|
—
|
|
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
Deaths
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
AEs that led to discontinuation
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: All treated participants
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=7 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
n=4 Participants
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
n=12 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
n=7 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
n=5 Participants
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
|
91 percentage of participants
Interval 58.7 to 99.8
|
86 percentage of participants
Interval 42.1 to 99.6
|
100 percentage of participants
Interval 39.8 to 100.0
|
83 percentage of participants
Interval 51.6 to 97.9
|
86 percentage of participants
Interval 42.1 to 99.6
|
80 percentage of participants
Interval 28.4 to 99.5
|
SECONDARY outcome
Timeframe: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first metPopulation: Treated participants - responders
Time to MCyR is defined as the time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met. MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Ph+ Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=6 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=11 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Time to Major Cytogenetic Response (MCyR)
|
5.5 months
Interval 5.3 to 5.6
|
4.2 months
Interval 2.8 to 5.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration.Population: Blood samples were collected for PK to be included in separate population PK analyses. No study specific PK analyses were planned for this report.
Blood sample collection for pharmacokinetic (PK) analysis that will contribute to PK modeling.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or deathPopulation: Median duration was not reached at the time of this report; see Outcome Measure 14 for corresponding life table.
The duration of MCyR will be measured from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death. Subjects who neither progress nor die will be censored on the date of their last cytogenetic assessment.MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Philadelphia-positive (Ph+) Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are metPopulation: Treated participants - responders
Time to CHR = time from first dose of Dasatinib until the first day CHR criteria are met (provided subjects achieved a cCHR). CHR=all of the following criteria: white blood cell count ≤ upper limit of normal; 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. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=10 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=10 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Time to CHR
|
1.0 months
Interval 0.5 to 1.1
|
0.6 months
Interval 0.5 to 0.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until deathPopulation: Median duration of CHR was not reach at the time of this report. See corresponding life table presented in Outcome Measure 15.
The duration of CHR were measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death. Subjects who neither progress nor die were censored on the date of their last hematologic assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first metPopulation: Median months of progression-free survival was not reached at the time of this report. See corresponding life table in Outcome Measure 16.
Progressed disease=achieving a CHR \& subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose \& increase in white blood cell count (doubling of count from lowest value to \>20,000/mm3 or an increase by \>50,000/mm3 on 2 assessments done ≥2 weeks apart); meeting the criteria of accelerated or blastic phase chronic myeloid leukemia at any time; having an MCyR \& subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a \>=30% absolute increase in number of Ph+ metaphases.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)Population: Treated participants
Number of participants with positive (\>= 2.0 log copies/mg) and negative (\<2.0 log copies/mg) expression of mRNA at Baseline and at end of study.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=12 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Positive at Baseline
|
11 participants
|
11 participants
|
—
|
—
|
—
|
—
|
|
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Negative at Baseline
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Positive at End-of-Study
|
8 participants
|
3 participants
|
—
|
—
|
—
|
—
|
|
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Negative at End-of-Study
|
3 participants
|
9 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)Population: Treated participants
Number of participants with a particular BCR-ABL mutation at Baseline and End-of-Study.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=12 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Mutational Spectrum of BCR-ABL
G250E mutation at Baseline
|
1 participants
|
3 participants
|
—
|
—
|
—
|
—
|
|
Mutational Spectrum of BCR-ABL
G250E mutation at End-of-Study
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Mutational Spectrum of BCR-ABL
F317L mutation at Baseline
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Mutational Spectrum of BCR-ABL
F317L mutation at End-of-Study
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Mutational Spectrum of BCR-ABL
T315I mutation at Baseline
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Mutational Spectrum of BCR-ABL
T315I mutation at End-of-Study
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)Population: All treated participants
Cytogenetic response (CyR) as reflected in the major cytogenetic response was determined by bone marrow (BM) aspirates and are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each BM sample. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), or Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=12 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
MCyR
|
55 percentage of participants
Interval 23.4 to 83.3
|
92 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
—
|
—
|
|
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
CCyR
|
36 percentage of participants
Interval 10.9 to 69.2
|
67 percentage of participants
Interval 34.9 to 90.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)Population: All treated participants
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=11 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=12 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
|
91 percentage of participants
Interval 58.7 to 99.8
|
83 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Months 0, 4, 8, 12, 16, 20, 24Population: Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 6)
MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Ph+ Cells in Metaphase in BM: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=6 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=11 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 0
|
6 participants
|
11 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 4
|
6 participants
|
9 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 8
|
6 participants
|
9 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 12
|
4 participants
|
8 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 16
|
3 participants
|
3 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 20
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
Month 24
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Months 0, 4, 8, 12, 16, 20, 24Population: Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 7)
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; 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. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=6 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=11 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 0
|
10 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 4
|
9 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 8
|
9 participants
|
8 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 12
|
9 participants
|
8 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 16
|
8 participants
|
7 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 20
|
4 participants
|
4 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
Month 24
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Months 0, 4, 8, 12, 16, 20, 24Population: Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 7)
Progressed disease=achieving a CHR and subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose and an increase in white blood cell count (doubling of the count from lowest value to \>20,000/mm3 or an increase by \>50,000/mm3 on 2 assessments done at least 2 weeks apart); meeting the criteria of accelerated or blastic phase CML at any time; having an MCyR and subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a \>=30% absolute increase in number of Ph+ metaphases.
Outcome measures
| Measure |
Dasatinib 100 mg QD Starting Dose Cohort
n=6 Participants
All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-resistant
n=11 Participants
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose Cohort
All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-resistant
Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 0
|
11 participants
|
12 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 4
|
11 participants
|
12 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 8
|
9 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 12
|
9 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 16
|
9 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 20
|
7 participants
|
7 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
Month 24
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
Adverse Events
Dasatinib 100 mg Once-daily (QD) Starting Dose
Serious events: 4 serious events
Other events: 11 other events
Deaths: 0 deaths
Dasatinib 50 mg Twice-daily (BID) Starting Dose
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Total
Serious events: 10 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib 100 mg Once-daily (QD) Starting Dose
n=11 participants at risk
Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Dasatinib 50 mg Twice-daily (BID) Starting Dose
n=12 participants at risk
Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Total
n=23 participants at risk
|
|---|---|---|---|
|
Gastrointestinal disorders
Enterocolitis
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/23
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
General disorders
Pyrexia
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Infections and infestations
Pneumonia
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Infections and infestations
Gastroenteritis viral
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Metabolism and nutrition disorders
Glucose tolerance impaired
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
Other adverse events
| Measure |
Dasatinib 100 mg Once-daily (QD) Starting Dose
n=11 participants at risk
Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Dasatinib 50 mg Twice-daily (BID) Starting Dose
n=12 participants at risk
Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
|
Total
n=23 participants at risk
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
54.5%
6/11
|
50.0%
6/12
|
52.2%
12/23
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Cardiac disorders
Pericardial effusion
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Ear and labyrinth disorders
Eustachian tube obstruction
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Eye disorders
Eyelid oedema
|
27.3%
3/11
|
8.3%
1/12
|
17.4%
4/23
|
|
Eye disorders
Cataract
|
18.2%
2/11
|
0.00%
0/12
|
8.7%
2/23
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Eye disorders
Retinopathy
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Diarrhoea
|
36.4%
4/11
|
41.7%
5/12
|
39.1%
9/23
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11
|
41.7%
5/12
|
26.1%
6/23
|
|
Gastrointestinal disorders
Dental caries
|
27.3%
3/11
|
8.3%
1/12
|
17.4%
4/23
|
|
Gastrointestinal disorders
Gastritis
|
36.4%
4/11
|
0.00%
0/12
|
17.4%
4/23
|
|
Gastrointestinal disorders
Stomatitis
|
18.2%
2/11
|
16.7%
2/12
|
17.4%
4/23
|
|
Gastrointestinal disorders
Nausea
|
18.2%
2/11
|
8.3%
1/12
|
13.0%
3/23
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Gastric ulcer
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Gingival bleeding
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Oedema mouth
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Stomach discomfort
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Gastrointestinal disorders
Gastric dysplasia
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
General disorders
Pyrexia
|
18.2%
2/11
|
33.3%
4/12
|
26.1%
6/23
|
|
General disorders
Oedema peripheral
|
18.2%
2/11
|
16.7%
2/12
|
17.4%
4/23
|
|
General disorders
Malaise
|
18.2%
2/11
|
8.3%
1/12
|
13.0%
3/23
|
|
General disorders
Chest pain
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
General disorders
Face oedema
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
General disorders
Oedema
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
General disorders
Fatigue
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
General disorders
Feeling abnormal
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
General disorders
Feeling hot
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
General disorders
Localised oedema
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Infections and infestations
Nasopharyngitis
|
63.6%
7/11
|
83.3%
10/12
|
73.9%
17/23
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
Infections and infestations
Pharyngitis
|
18.2%
2/11
|
0.00%
0/12
|
8.7%
2/23
|
|
Infections and infestations
Urinary tract infection
|
18.2%
2/11
|
0.00%
0/12
|
8.7%
2/23
|
|
Infections and infestations
Bronchitis
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Infections and infestations
Rhinitis
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Infections and infestations
Enteritis infectious
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Investigations
Platelet count decreased
|
72.7%
8/11
|
58.3%
7/12
|
65.2%
15/23
|
|
Investigations
Neutrophil count decreased
|
63.6%
7/11
|
58.3%
7/12
|
60.9%
14/23
|
|
Investigations
White blood cell count decreased
|
45.5%
5/11
|
58.3%
7/12
|
52.2%
12/23
|
|
Investigations
Alanine aminotransferase increased
|
27.3%
3/11
|
50.0%
6/12
|
39.1%
9/23
|
|
Investigations
Lymphocyte count decreased
|
45.5%
5/11
|
33.3%
4/12
|
39.1%
9/23
|
|
Investigations
Blood creatine phosphokinase increased
|
9.1%
1/11
|
41.7%
5/12
|
26.1%
6/23
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/11
|
41.7%
5/12
|
21.7%
5/23
|
|
Investigations
Blood phosphorus decreased
|
27.3%
3/11
|
16.7%
2/12
|
21.7%
5/23
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
1/11
|
25.0%
3/12
|
17.4%
4/23
|
|
Investigations
Blood albumin decreased
|
27.3%
3/11
|
8.3%
1/12
|
17.4%
4/23
|
|
Investigations
Blood creatinine increased
|
27.3%
3/11
|
8.3%
1/12
|
17.4%
4/23
|
|
Investigations
Red blood cell count decreased
|
9.1%
1/11
|
25.0%
3/12
|
17.4%
4/23
|
|
Investigations
Blood sodium decreased
|
18.2%
2/11
|
8.3%
1/12
|
13.0%
3/23
|
|
Investigations
Haemoglobin decreased
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Investigations
Liver function test abnormal
|
0.00%
0/11
|
25.0%
3/12
|
13.0%
3/23
|
|
Investigations
Weight decreased
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Investigations
Blood alkaline phosphatase increased
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Investigations
Blood potassium decreased
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Investigations
Blood urea increased
|
18.2%
2/11
|
0.00%
0/12
|
8.7%
2/23
|
|
Investigations
Blood uric acid increased
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
Investigations
Weight increased
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Investigations
Protein urine present
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Investigations
Blood calcium decreased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Blood fibrinogen increased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Blood folate decreased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Blood potassium increased
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Investigations
Blood pressure decreased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
C-reactive protein increased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Haematocrit decreased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Intraocular pressure increased
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Investigations
Lymphocyte count increased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Investigations
Neutrophil count increased
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Investigations
Protein total increased
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Investigations
Vitamin B12 decreased
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
9.1%
1/11
|
16.7%
2/12
|
13.0%
3/23
|
|
Metabolism and nutrition disorders
Anorexia
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
27.3%
3/11
|
25.0%
3/12
|
26.1%
6/23
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Nervous system disorders
Headache
|
18.2%
2/11
|
25.0%
3/12
|
21.7%
5/23
|
|
Nervous system disorders
Carpal tunnel syndrome
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Nervous system disorders
Dizziness postural
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Psychiatric disorders
Insomnia
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Psychiatric disorders
Apathy
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Reproductive system and breast disorders
Gynaecomastia
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
36.4%
4/11
|
50.0%
6/12
|
43.5%
10/23
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.3%
3/11
|
33.3%
4/12
|
30.4%
7/23
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
27.3%
3/11
|
16.7%
2/12
|
21.7%
5/23
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
1/11
|
8.3%
1/12
|
8.7%
2/23
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal discomfort
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Rash
|
45.5%
5/11
|
75.0%
9/12
|
60.9%
14/23
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/11
|
16.7%
2/12
|
8.7%
2/23
|
|
Skin and subcutaneous tissue disorders
Skin depigmentation
|
18.2%
2/11
|
0.00%
0/12
|
8.7%
2/23
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/11
|
8.3%
1/12
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
|
Vascular disorders
Hypertension
|
18.2%
2/11
|
8.3%
1/12
|
13.0%
3/23
|
|
Vascular disorders
Hypotension
|
9.1%
1/11
|
0.00%
0/12
|
4.3%
1/23
|
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