Leukemia
Conditions
Keywords
Leukemia, Pediatric
Brief summary
The purpose of this study is to determine whether dasatinib is safe and effective in children and adolescents with newly diagnosed chronic myeloid leukemia (CML), or in children with Ph+ acute lymphoblastic leukemia (ALL), accelerated or blast phases CML who relapse after imatinib or who are resistant or intolerant to imatinib. The side effects of this oral investigational drug in children and adolescents will be evaluated
Interventions
DRUGDasatinib
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * CP-CML who prove resistant or intolerant to imatinib (Cohort 1) * Ph+ ALL, AP-CML, or BP-CML who are resistant or intolerant to or who relapse after imatinib therapy (Cohort 2) * Newly diagnosed, treatment naive CP-CML (Cohort 3) * Lansky or Karnofsky scale \>50 * Life expectancy ≥12 weeks * Adequate hepatic and renal function * Written informed consent * Target Population for the PK substudy must obtain written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation * Target Population for the PK substudy subjects must have CP-CML and be taking daily dasatinib (tablets or PFOS) either as part of Cohort 1 or Cohort 3 of this protocol. Patients receiving commercial dasatinib tablets outside of this protocol may be invited to participate in this PK substudy * Target Population for the PK substudy subjects with CP-CML who are tolerating dasatinib tablet dose of at least 60 mg/m2 or dasatinib PFOS dose of at least 72 mg/m2 * Target Population for the PK substudy prior exposure to imatinib or other TKI therapy is permissible * Target Population for the PK substudy subjects must meet relevant inclusion criteria
Exclusion criteria
* Eligibility for potentially-curative therapy including hematopoietic stem-cell transplantation * Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease) * Isolated extramedullary disease * Prior therapy with Dasatinib * Target Population for the PK substudy subjects participating in the PK substudy must comply with the relevant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Cytogenetic Response (MCyR) Rate | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method. |
| Complete Hematologic Response (CHR) Rate | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method. |
| Complete Cytogenetic Response (CCyR) Rate | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Major Cytogenetic Response (MCyR) | From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months) | Time to MCyR is defined as the time from first dose of dasatinib until the first day MCyR criteria are met, computed only for participants whose best response is MCyR. (Based on \>=20 Metaphases) |
| Duration of Major Cytogenetic Response (MCyR) | From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months) | Duration of MCyR will be computed from the first day criteria are met for MCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases) |
| Time to Complete Cytogenetic Response (CCyR) | From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months) | Time to CCyR is defined as the time from first dose of dasatinib until the first day CCyR criteria are met, computed only for participants whose best response is CCyR. (Based on \>=20 Metaphases) |
| Duration of Complete Cytogenetic Response (CCyR) | From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months) | Duration of CCyR will be computed from the first day criteria are met for CCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases) |
| Progression-Free Survival (PFS) | 174 Months | PFS is defined as time from the first dosing date until the time PD is first documented by the investigator or death. Participants who die without a reported date of progression will be considered to have progressed on the date of death. Participants who neither progress nor die will be censored on the date of their last cytogenetic or hematologic assessment. Based on Kaplan-Meier methodology. Disease Progression was defined as any of the following criteria: -For CP-CML, progression to AP-CML or BP-CML while at highest tolerated dose -Increasing WBC -Loss of CHR (defined as any of the following: WBC count rises to \>20.0x10\^9/L; Platelet count rises to \>600x10\^9/L; appearance of extramedullary disease; appearance of \>5% myelocytes+metamyelocytes in blood; appearance of blasts/promyelocytes in peripheral blood) -Loss of MCyR or increase in Ph+ bone marrow cells by \>=30% from nadir -Death from any case during treatment. |
| Time to Complete Hematologic Response (CHR) | From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months) | Time to CHR is defined as the time from first dose of dasatinib until the first day CHR criteria are met, provided they are confirmed 4 weeks later, computed only for participants whose best response is CHR. |
| Duration of Complete Hemotologic Response (CHR) | From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months) | Duration of CHR will be computed from the first day all criteria are met for CHR, provided they are confirmed 4 weeks later, until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic assessment. |
| Major Cytogenetic Response (MCyR) Rate in Cohort 2 | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | Major Cytogenetic Response (MCyR) rate was defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants in each arm with MCyR is reported. |
| Overall Survival (OS) | 174 Months | OS is defined as time from the first dosing date until the time of death. All participants will be followed yearly for survival for up to 5 years after treatment discontinuation. Participants who have not died or who are lost to follow-up will be censored on the last date the participant is known to be alive. Based on Kaplan-Meier methodology using graphs. |
| Major Molecular Response (MMR) Rate | From date of first treatment to date of MMR (assessed up to Jan 2025, approximately 15 years and 10 months) | Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). MMR for participants with the p210 BCR-ABL transcript variant was defined as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale. In this study, ABL was used as the control-gene. For a participant with the p190 BCR-ABL transcript variant (occurring in Cohort 2 only), on-study assessments were compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline was considered an MMR. |
| Complete Molecular Response (CMR) Rate | From date of first treatment to date of CMR (assessed up to Jan 2025, approximately 15 years and 10 months) | Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm. |
| Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants with MCyR is reported by arm. |
| Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The percentage of treated participants with CCyR is reported by arm. |
| Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time qPCR. MMR for participants with the p210 BCR-ABL transcript variant is defined according to the recommendations of Hughes et al. as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale proposed by the authors. The standardized baseline, as established in the IRIS trial, is taken to represent 100% on the international scale and a 3-log reduction in ratio (BCR-ABL transcripts/ABL or BCR) from the standardized baseline (MMR) is fixed at 0.1%. In this study, ABL or other housekeeping gene, will be used as the control-gene. For a participant with the p190 BCR-ABL transcript variant, on-study assessments will be compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline will be considered an MMR. The percentage of treated participants with MMR is reported by arm. |
| Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm. |
| Disease-Free Survival | 168 Months | Disease free survival is defined as time from CCyR for participants with newly diagnosed chronic phase CML and for participants with chronic phase CML who are resistant or intolerant to imatinib (cohort 3 and cohort 1), and as time from CHR for participants with advanced phase CML and PH + ALL (cohort 2) until the time progression is first documented by the investigator or death from any cause. Based on Kaplan-Meier methodology. (CML: Chronic Myeloid Leukemia). |
| Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3 | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | Complete Hematologic Response (CHR) rate defined as the proportion of all treated participants who achieve a confirmed CHR while on-study. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood. The percentage of treated participants in each arm with CHR is reported. |
| Rate of Best Cytogenetic Response | From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months) | The number of participants achieving their best on-study cytogenetic response was reported as a percentage of all treated participants in that arm. (Based on \>=20 Metaphases) |
Countries
Argentina, Australia, Brazil, Canada, France, Germany, India, Italy, Mexico, Netherlands, Romania, Russia, Singapore, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 80 sites (Argentina, Australia, Brazil, Canada, France, Germany, Great Britain, India, Italy, Korea, Mexico, Netherlands, Romania, Russia, Singapore, South Africa, Spain, and USA).
Pre-assignment details
The PK sub-study analysis is not part of the pre-specified primary and secondary outcome measures.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen. | 29 |
| Cohort 2 Children and adolescents with Ph+ ALL, AP-CML or BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen. | 17 |
| Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen. | 84 |
| PK Sub-Study Children and adolescents received powder for oral suspension (PFOS) at a dose of 90 mg/m2 QD to evaluate the pharmacokinetics of dasatinib. | 3 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up | Death | 1 | 9 | 0 | 0 |
| Follow-Up | Lost to Follow-up | 3 | 0 | 0 | 0 |
| Follow-Up | Missing - Administrative Reasons in Russia | 1 | 0 | 4 | 0 |
| Follow-Up | Reason Not Specified | 4 | 0 | 13 | 0 |
| Follow-Up | Withdrawal by Subject | 0 | 0 | 5 | 0 |
| On Treatment | Administrative Reason By Sponsor | 1 | 0 | 9 | 0 |
| On Treatment | Death | 0 | 2 | 0 | 0 |
| On Treatment | Failure to Meet Study Criteria | 0 | 1 | 4 | 0 |
| On Treatment | Maximum Clinical Benefit | 2 | 0 | 5 | 0 |
| On Treatment | Non-compliance with Study Drug | 1 | 0 | 1 | 0 |
| On Treatment | Not Reported | 0 | 0 | 2 | 0 |
| On Treatment | Participant Request to Discontinue Study Treatment | 4 | 0 | 6 | 0 |
| On Treatment | Pregnancy | 1 | 0 | 1 | 0 |
| On Treatment | Progressive Disease | 6 | 4 | 7 | 0 |
| On Treatment | Reached 18 years of age and transitioned to commercial drug | 13 | 7 | 42 | 0 |
| On Treatment | Site Closed | 0 | 1 | 1 | 0 |
| On Treatment | Study Drug Toxicity | 1 | 0 | 4 | 0 |
| On Treatment | Withdrawal by Subject | 0 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | PK Sub-Study | Total |
|---|---|---|---|---|---|
| Age, Continuous | 12.60 years STANDARD_DEVIATION 4.774 | 12.10 years STANDARD_DEVIATION 3.68 | 11.95 years STANDARD_DEVIATION 4.418 | 13.33 years STANDARD_DEVIATION 1.154 | 12.05 years STANDARD_DEVIATION 4.255 |
| Age, Customized >= 12 to < 18 years | 17 participants | 9 participants | 44 participants | 3 participants | 73 participants |
| Age, Customized >= 18 years | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Age, Customized >= 2 to < 7 years | 3 participants | 2 participants | 10 participants | 0 participants | 15 participants |
| Age, Customized < 2 years | 1 participants | 0 participants | 2 participants | 0 participants | 3 participants |
| Age, Customized >= 7 to < 12 years | 6 participants | 6 participants | 28 participants | 0 participants | 40 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 0 Participants | 20 Participants | 1 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 23 Participants | 17 Participants | 59 Participants | 2 Participants | 101 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 3 Participants | 23 Participants | 0 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 13 Participants | 56 Participants | 2 Participants | 91 Participants |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 39 Participants | 2 Participants | 66 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 45 Participants | 1 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 29 | 4 / 8 | 7 / 9 | 0 / 51 | 0 / 33 | 0 / 7 |
| other Total, other adverse events | 27 / 29 | 7 / 8 | 9 / 9 | 50 / 51 | 33 / 33 | 0 / 7 |
| serious Total, serious adverse events | 16 / 29 | 7 / 8 | 6 / 9 | 21 / 51 | 12 / 33 | 0 / 7 |
Outcome results
Primary
Complete Cytogenetic Response (CCyR) Rate
Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Complete Cytogenetic Response (CCyR) Rate | 94.0 percentage of participants |
Primary
Complete Hematologic Response (CHR) Rate
Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Complete Hematologic Response (CHR) Rate | 29.4 percentage of participants |
Primary
Major Cytogenetic Response (MCyR) Rate
Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Major Cytogenetic Response (MCyR) Rate | 89.7 percentage of participants |
Secondary
Complete Cytogenetic Response (CCyR) Rate up to 2 Years
Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The percentage of treated participants with CCyR is reported by arm.
Time frame: 24 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | 82.8 percentage of participants |
| Cohort 1 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 12 months | 75.9 percentage of participants |
| Cohort 3 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | 41.2 percentage of participants |
| Cohort 3 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 12 months | 41.2 percentage of participants |
| Cohort 3 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | 94.0 percentage of participants |
| Cohort 3 | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 12 months | 92.9 percentage of participants |
| Cohort 3a | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 12 months | 96.1 percentage of participants |
| Cohort 3a | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | 96.1 percentage of participants |
| Cohort 3b | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 24 months | 90.9 percentage of participants |
| Cohort 3b | Complete Cytogenetic Response (CCyR) Rate up to 2 Years | 12 months | 87.9 percentage of participants |
Secondary
Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3
Complete Hematologic Response (CHR) rate defined as the proportion of all treated participants who achieve a confirmed CHR while on-study. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood. The percentage of treated participants in each arm with CHR is reported.
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: Secondary efficacy endpoint pre-specified only for participants treated in Cohort 1 and Cohort 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3 | 93.1 percentage of participants |
| Cohort 3 | Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3 | 96.4 percentage of participants |
Secondary
Complete Molecular Response (CMR) Rate
Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.
Time frame: From date of first treatment to date of CMR (assessed up to Jan 2025, approximately 15 years and 10 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Complete Molecular Response (CMR) Rate | 27.6 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate | 42.9 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate | 49.0 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate | 33.3 percentage of participants |
Secondary
Complete Molecular Response (CMR) Rate up to 7.5 Years
Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.
Time frame: 90 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 12 months | 6.9 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 24 months | 17.2 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 36 months | 17.2 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 48 months | 24.1 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 60 months | 24.1 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 72 months | 24.1 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 84 months | 24.1 percentage of participants |
| Cohort 1 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | 27.6 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 36 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 72 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 12 months | 5.9 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 48 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 24 months | 5.9 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 60 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 84 months | 11.8 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 84 months | 42.9 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | 42.9 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 48 months | 34.5 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 72 months | 41.7 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 36 months | 28.6 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 24 months | 25.0 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 12 months | 8.3 percentage of participants |
| Cohort 3 | Complete Molecular Response (CMR) Rate up to 7.5 Years | 60 months | 40.5 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 24 months | 33.3 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 36 months | 33.3 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 48 months | 43.1 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 60 months | 47.1 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 72 months | 49.0 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | 49.0 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 12 months | 9.8 percentage of participants |
| Cohort 3a | Complete Molecular Response (CMR) Rate up to 7.5 Years | 84 months | 49.0 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 48 months | 21.2 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 90 months | 33.3 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 36 months | 21.2 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 84 months | 33.3 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 12 months | 6.1 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 72 months | 30.3 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 24 months | 12.1 percentage of participants |
| Cohort 3b | Complete Molecular Response (CMR) Rate up to 7.5 Years | 60 months | 30.3 percentage of participants |
Secondary
Disease-Free Survival
Disease free survival is defined as time from CCyR for participants with newly diagnosed chronic phase CML and for participants with chronic phase CML who are resistant or intolerant to imatinib (cohort 3 and cohort 1), and as time from CHR for participants with advanced phase CML and PH + ALL (cohort 2) until the time progression is first documented by the investigator or death from any cause. Based on Kaplan-Meier methodology. (CML: Chronic Myeloid Leukemia).
Time frame: 168 Months
Population: All treated participants with response of CCyR or CHR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Disease-Free Survival | NA Months |
| Cohort 3 | Disease-Free Survival | NA Months |
| Cohort 3 | Disease-Free Survival | NA Months |
| Cohort 3a | Disease-Free Survival | NA Months |
| Cohort 3b | Disease-Free Survival | NA Months |
Secondary
Duration of Complete Cytogenetic Response (CCyR)
Duration of CCyR will be computed from the first day criteria are met for CCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases)
Time frame: From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months)
Population: All treated participants who achieved CCyR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Complete Cytogenetic Response (CCyR) | NA months |
| Cohort 3 | Duration of Complete Cytogenetic Response (CCyR) | NA months |
| Cohort 3 | Duration of Complete Cytogenetic Response (CCyR) | NA months |
| Cohort 3a | Duration of Complete Cytogenetic Response (CCyR) | NA months |
| Cohort 3b | Duration of Complete Cytogenetic Response (CCyR) | NA months |
Secondary
Duration of Complete Hemotologic Response (CHR)
Duration of CHR will be computed from the first day all criteria are met for CHR, provided they are confirmed 4 weeks later, until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic assessment.
Time frame: From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months)
Population: All treated participants with CCyR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Complete Hemotologic Response (CHR) | NA months |
| Cohort 3 | Duration of Complete Hemotologic Response (CHR) | NA months |
| Cohort 3 | Duration of Complete Hemotologic Response (CHR) | NA months |
| Cohort 3a | Duration of Complete Hemotologic Response (CHR) | NA months |
| Cohort 3b | Duration of Complete Hemotologic Response (CHR) | NA months |
Secondary
Duration of Major Cytogenetic Response (MCyR)
Duration of MCyR will be computed from the first day criteria are met for MCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases)
Time frame: From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months)
Population: All treated participants with MCyR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Major Cytogenetic Response (MCyR) | NA months |
| Cohort 3 | Duration of Major Cytogenetic Response (MCyR) | 11.2 months |
| Cohort 3 | Duration of Major Cytogenetic Response (MCyR) | NA months |
| Cohort 3a | Duration of Major Cytogenetic Response (MCyR) | NA months |
| Cohort 3b | Duration of Major Cytogenetic Response (MCyR) | NA months |
Secondary
Major Cytogenetic Response (MCyR) Rate in Cohort 2
Major Cytogenetic Response (MCyR) rate was defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants in each arm with MCyR is reported.
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: Secondary efficacy endpoint pre-specified only for participants treated in Cohort 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Major Cytogenetic Response (MCyR) Rate in Cohort 2 | 52.9 percentage of participants |
Secondary
Major Cytogenetic Response (MCyR) Rate up to 2 Years
Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants with MCyR is reported by arm.
Time frame: 24 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 12 months | 89.7 percentage of participants |
| Cohort 1 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | 89.7 percentage of participants |
| Cohort 3 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 12 months | 58.8 percentage of participants |
| Cohort 3 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | 58.8 percentage of participants |
| Cohort 3 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 12 months | 96.4 percentage of participants |
| Cohort 3 | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | 96.4 percentage of participants |
| Cohort 3a | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | 98.0 percentage of participants |
| Cohort 3a | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 12 months | 98.0 percentage of participants |
| Cohort 3b | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 12 months | 93.9 percentage of participants |
| Cohort 3b | Major Cytogenetic Response (MCyR) Rate up to 2 Years | 24 months | 93.9 percentage of participants |
Secondary
Major Molecular Response (MMR) Rate
Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). MMR for participants with the p210 BCR-ABL transcript variant was defined as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale. In this study, ABL was used as the control-gene. For a participant with the p190 BCR-ABL transcript variant (occurring in Cohort 2 only), on-study assessments were compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline was considered an MMR.
Time frame: From date of first treatment to date of MMR (assessed up to Jan 2025, approximately 15 years and 10 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Major Molecular Response (MMR) Rate | 69.0 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate | 84.5 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate | 90.2 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate | 75.8 percentage of participants |
Secondary
Major Molecular Response (MMR) Rate up to 7.5 Years
Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time qPCR. MMR for participants with the p210 BCR-ABL transcript variant is defined according to the recommendations of Hughes et al. as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale proposed by the authors. The standardized baseline, as established in the IRIS trial, is taken to represent 100% on the international scale and a 3-log reduction in ratio (BCR-ABL transcripts/ABL or BCR) from the standardized baseline (MMR) is fixed at 0.1%. In this study, ABL or other housekeeping gene, will be used as the control-gene. For a participant with the p190 BCR-ABL transcript variant, on-study assessments will be compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline will be considered an MMR. The percentage of treated participants with MMR is reported by arm.
Time frame: 90 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 12 months | 41.4 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 24 months | 55.2 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 36 months | 62.1 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 48 months | 62.1 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 60 months | 65.5 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 72 months | 65.5 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 84 months | 65.5 percentage of participants |
| Cohort 1 | Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | 69.0 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 36 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 72 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 12 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 48 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 24 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 60 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 84 months | 29.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 84 months | 84.5 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | 84.5 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 48 months | 82.1 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 72 months | 84.5 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 36 months | 77.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 24 months | 70.2 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 12 months | 52.4 percentage of participants |
| Cohort 3 | Major Molecular Response (MMR) Rate up to 7.5 Years | 60 months | 83.3 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 24 months | 74.5 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 36 months | 82.4 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 48 months | 88.2 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 60 months | 90.2 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 72 months | 90.2 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | 90.2 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 12 months | 56.9 percentage of participants |
| Cohort 3a | Major Molecular Response (MMR) Rate up to 7.5 Years | 84 months | 90.2 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 48 months | 72.7 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 90 months | 75.8 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 36 months | 69.7 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 84 months | 75.8 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 12 months | 45.5 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 72 months | 75.8 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 24 months | 63.6 percentage of participants |
| Cohort 3b | Major Molecular Response (MMR) Rate up to 7.5 Years | 60 months | 72.7 percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as time from the first dosing date until the time of death. All participants will be followed yearly for survival for up to 5 years after treatment discontinuation. Participants who have not died or who are lost to follow-up will be censored on the last date the participant is known to be alive. Based on Kaplan-Meier methodology using graphs.
Time frame: 174 Months
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Overall Survival (OS) | NA Months |
| Cohort 3 | Overall Survival (OS) | 13.63 Months |
| Cohort 3 | Overall Survival (OS) | NA Months |
| Cohort 3a | Overall Survival (OS) | NA Months |
| Cohort 3b | Overall Survival (OS) | NA Months |
Secondary
Progression-Free Survival (PFS)
PFS is defined as time from the first dosing date until the time PD is first documented by the investigator or death. Participants who die without a reported date of progression will be considered to have progressed on the date of death. Participants who neither progress nor die will be censored on the date of their last cytogenetic or hematologic assessment. Based on Kaplan-Meier methodology. Disease Progression was defined as any of the following criteria: -For CP-CML, progression to AP-CML or BP-CML while at highest tolerated dose -Increasing WBC -Loss of CHR (defined as any of the following: WBC count rises to \>20.0x10\^9/L; Platelet count rises to \>600x10\^9/L; appearance of extramedullary disease; appearance of \>5% myelocytes+metamyelocytes in blood; appearance of blasts/promyelocytes in peripheral blood) -Loss of MCyR or increase in Ph+ bone marrow cells by \>=30% from nadir -Death from any case during treatment.
Time frame: 174 Months
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression-Free Survival (PFS) | NA Months |
| Cohort 3 | Progression-Free Survival (PFS) | 6.67 Months |
| Cohort 3 | Progression-Free Survival (PFS) | NA Months |
| Cohort 3a | Progression-Free Survival (PFS) | NA Months |
| Cohort 3b | Progression-Free Survival (PFS) | NA Months |
Secondary
Rate of Best Cytogenetic Response
The number of participants achieving their best on-study cytogenetic response was reported as a percentage of all treated participants in that arm. (Based on \>=20 Metaphases)
Time frame: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Rate of Best Cytogenetic Response | Complete (0%) | 82.8 percentage of participants |
| Cohort 1 | Rate of Best Cytogenetic Response | Partial (>0% - 35%) | 6.9 percentage of participants |
| Cohort 1 | Rate of Best Cytogenetic Response | Minor (>35% - 65%) | 3.4 percentage of participants |
| Cohort 1 | Rate of Best Cytogenetic Response | Minimal (>65% - 95%) | 3.4 percentage of participants |
| Cohort 1 | Rate of Best Cytogenetic Response | No Response (>95% - 100%) | 0 percentage of participants |
| Cohort 1 | Rate of Best Cytogenetic Response | Unable to Determine | 3.4 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | No Response (>95% - 100%) | 5.9 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Unable to Determine | 41.2 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Complete (0%) | 29.4 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Minor (>35% - 65%) | 0 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Minimal (>65% - 95%) | 0 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Partial (>0% - 35%) | 23.5 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Minimal (>65% - 95%) | 1.2 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | No Response (>95% - 100%) | 0 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Complete (0%) | 94.0 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Minor (>35% - 65%) | 0 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Partial (>0% - 35%) | 2.4 percentage of participants |
| Cohort 3 | Rate of Best Cytogenetic Response | Unable to Determine | 2.4 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | Minimal (>65% - 95%) | 2.0 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | Partial (>0% - 35%) | 2.0 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | Minor (>35% - 65%) | 0 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | Unable to Determine | 0 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | No Response (>95% - 100%) | 0 percentage of participants |
| Cohort 3a | Rate of Best Cytogenetic Response | Complete (0%) | 96.1 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | No Response (>95% - 100%) | 0 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | Minor (>35% - 65%) | 0 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | Partial (>0% - 35%) | 3.0 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | Unable to Determine | 6.1 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | Minimal (>65% - 95%) | 0 percentage of participants |
| Cohort 3b | Rate of Best Cytogenetic Response | Complete (0%) | 90.9 percentage of participants |
Secondary
Time to Complete Cytogenetic Response (CCyR)
Time to CCyR is defined as the time from first dose of dasatinib until the first day CCyR criteria are met, computed only for participants whose best response is CCyR. (Based on \>=20 Metaphases)
Time frame: From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months)
Population: All treated participants with CCyR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Complete Cytogenetic Response (CCyR) | 3.9 months |
| Cohort 3 | Time to Complete Cytogenetic Response (CCyR) | 1.6 months |
| Cohort 3 | Time to Complete Cytogenetic Response (CCyR) | 5.6 months |
| Cohort 3a | Time to Complete Cytogenetic Response (CCyR) | 5.7 months |
| Cohort 3b | Time to Complete Cytogenetic Response (CCyR) | 5.6 months |
Secondary
Time to Complete Hematologic Response (CHR)
Time to CHR is defined as the time from first dose of dasatinib until the first day CHR criteria are met, provided they are confirmed 4 weeks later, computed only for participants whose best response is CHR.
Time frame: From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months)
Population: All treated participants with CHR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Complete Hematologic Response (CHR) | 0.7 months |
| Cohort 3 | Time to Complete Hematologic Response (CHR) | 2.5 months |
| Cohort 3 | Time to Complete Hematologic Response (CHR) | 1.2 months |
| Cohort 3a | Time to Complete Hematologic Response (CHR) | 1.2 months |
| Cohort 3b | Time to Complete Hematologic Response (CHR) | 1.0 months |
Secondary
Time to Major Cytogenetic Response (MCyR)
Time to MCyR is defined as the time from first dose of dasatinib until the first day MCyR criteria are met, computed only for participants whose best response is MCyR. (Based on \>=20 Metaphases)
Time frame: From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months)
Population: All treated participants with MCyR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Major Cytogenetic Response (MCyR) | 3.1 months |
| Cohort 3 | Time to Major Cytogenetic Response (MCyR) | 1.6 months |
| Cohort 3 | Time to Major Cytogenetic Response (MCyR) | 3.0 months |
| Cohort 3a | Time to Major Cytogenetic Response (MCyR) | 3.3 months |
| Cohort 3b | Time to Major Cytogenetic Response (MCyR) | 3.0 months |