Chronic Phase Chronic Myeloid Leukemia
Conditions
Keywords
CML, CP-CML, Leukemia, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplasms by Histologic Type, Neoplasms, Myeloproliferative Disorders, Bone Marrow Diseases, Hematologic Diseases
Brief summary
The purpose of this study is to compare the efficacy and safety of 2 starting doses of ponatinib compared to nilotinib in participants with imatinib-resistant chronic myeloid leukemia (CML) in chronic phase (CP).
Detailed description
This is a multi-center, randomized study to demonstrate the efficacy and safety of 2 starting doses of ponatinib as a treatment for CP-CML compared to nilotinib. Eligible participants must have chronic phase chronic myeloid leukemia (CP-CML), be resistant to first-line imatinib treatment and have received no other tyrosine kinase inhibitors (TKIs).
Interventions
DRUGPonatinib 30 mg QD
Ponatinib 30 mg, taken orally once daily.
DRUGPonatinib 15 mg QD
Ponatinib 15 mg, taken orally once daily.
DRUGNilotinib 400 mg BID
Nilotinib 400 mg, taken orally twice daily.
Sponsors
Ariad Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have CP-CML and are resistant to first-line imatinib treatment. 2. Be male or female ≥18 years old. 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Have adequate renal function as defined by the following criterion: • Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution. 5. Have adequate hepatic function as defined by all of the following criteria: * Total serum bilirubin ≤1.5 × ULN, unless due to Gilbert's syndrome * Alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present * Aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present. 6. Have normal pancreatic status as defined by the following criterion: * Serum lipase and amylase ≤1.5 × ULN.
Exclusion criteria
1. Have previously been treated with any approved or investigational TKIs other than imatinib or treated with imatinib within 14 days prior to receiving study drug. 2. Have previously been treated with any anti-CML therapy other than hydroxyurea, including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy, radiotherapy, or investigational therapy. 3. Underwent autologous or allogeneic stem cell transplant. 4. Are in CCyR or MMR. 5. Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: * Any history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (TIA) * Any history of peripheral vascular infarction, including visceral infarction * Any history of a revascularization procedure, including vascular surgery or the placement of a stent * History of venous thromboembolism, including deep venous thrombosis, superficial venous thrombosis, or pulmonary embolism, within 6 months prior to enrollment * Congestive heart failure (New York Heart Association \[NYHA\] class III or IV) within 6 months prior to enrollment or left ventricular ejection fraction (LVEF) less than 45% or less than the institutional lower limit of normal (whichever is higher) within 6 months prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Major Molecular Response (MMR) | Up to 12 months | MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) at any time within 12 months after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Cytogenetic Response (CCyR) | Up to 12 months | CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow. |
| Percentage of Participants With Molecular Response (MR) | From Month 3 to every 3 months up to 48 months | Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL\[IS\]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL\[IS\]), and MR4.5 (defined as ≤0.0032% BCR-ABL\[IS\]) after randomization. |
| Percentage of Participants With MR1 | Month 3 | MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months. |
| Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | From first dose up to 30 days post last dose (Up to approximately 46 months) | TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event. |
| Time to Response | Up to approximately 60 months | Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as \<=0.1% BCR-ABL. |
| Percentage of Participants With Major Cytogenetic Response (MCyR) | Up to 12 months | MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization. |
| Progression-free Survival (PFS) | Up to end of study (approximately 60 months) | Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment. |
| Overall Survival | Up to end of study (approximately 60 months) | Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive. |
| Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | 3 months after the first dose of study treatment | CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \<450 x 10\^9/L; No blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood \<5%; No extramedullary involvement (including no hepatomegaly or splenomegaly). |
| Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | From first dose up to end of treatment (Up to approximately 45 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. |
| Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML | Up to end of study (Up to approximately 60 months) | Progression to AP is defined as: \>=15% and \<30% blasts in peripheral blood or bone marrow or \>=20% basophils in peripheral blood or bone marrow or \>=30% blasts + promyelocytes in peripheral blood or bone marrow (but \<30% blasts) or \<100\*10\^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: \>=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. |
| Duration of Response | Up to approximately 60 months | Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met. |
Countries
Belgium
Participant flow
Recruitment details
Participants took part in the study at 90 investigative sites in Austria, Canada, Czechia, France, Hungary, Italy, Korea, and Russia from 31 December 2015 to 20 January 2021
Pre-assignment details
Participants with a diagnosis of chronic phase-chronic myeloid leukemia were enrolled and randomised at a ratio of 1:2:1 to receive ponatinib 30 mg and ponatinib 15 mg compared with nilotinib 400 mg.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Ponatinib 30 mg Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months. | 10 |
| Cohort B: Ponatinib 15 mg Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months. | 21 |
| Cohort C: Nilotinib 400 mg Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. | 12 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse event (not progressive disease) | 1 | 4 | 1 |
| Overall Study | Lack of Efficacy | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 2 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Progressive disease | 1 | 3 | 0 |
| Overall Study | Randomized but not Treated | 1 | 0 | 0 |
| Overall Study | Reason not Specified | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 5 | 10 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort A: Ponatinib 30 mg | Cohort B: Ponatinib 15 mg | Cohort C: Nilotinib 400 mg |
|---|---|---|---|---|
| Age, Continuous | 47.16 years STANDARD_DEVIATION 15.69 | 43.7 years STANDARD_DEVIATION 17.43 | 44.7 years STANDARD_DEVIATION 15.53 | 54.3 years STANDARD_DEVIATION 13.23 |
| Body Mass Index (BMI) | 25.44 kg/m^2 STANDARD_DEVIATION 4.95 | 25.90 kg/m^2 STANDARD_DEVIATION 5.87 | 25.35 kg/m^2 STANDARD_DEVIATION 4.974 | 25.18 kg/m^2 STANDARD_DEVIATION 4.442 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 10 Participants | 21 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.1 cm STANDARD_DEVIATION 9.28 | 172.9 cm STANDARD_DEVIATION 9.62 | 169.4 cm STANDARD_DEVIATION 9.35 | 168.8 cm STANDARD_DEVIATION 9.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 2 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 33 Participants | 7 Participants | 16 Participants | 10 Participants |
| Region of Enrollment Austria | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Canada | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Czech Republic | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment France | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Hungary | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Italy | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Korea, North | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Russia | 31 Participants | 8 Participants | 16 Participants | 7 Participants |
| Sex: Female, Male Female | 20 Participants | 3 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 23 Participants | 7 Participants | 10 Participants | 6 Participants |
| Weight | 73.34 kg STANDARD_DEVIATION 15.65 | 77.50 kg STANDARD_DEVIATION 18.335 | 72.72 kg STANDARD_DEVIATION 15.213 | 70.94 kg STANDARD_DEVIATION 14.711 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 10 | 1 / 21 | 0 / 12 |
| other Total, other adverse events | 10 / 10 | 20 / 21 | 12 / 12 |
| serious Total, serious adverse events | 4 / 10 | 3 / 21 | 2 / 12 |
Outcome results
Primary
Percentage of Participants With Major Molecular Response (MMR)
MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) at any time within 12 months after randomization.
Time frame: Up to 12 months
Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Major Molecular Response (MMR) | 50.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Major Molecular Response (MMR) | 33.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Major Molecular Response (MMR) | 45.5 percentage of participants |
Secondary
Duration of Response
Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met.
Time frame: Up to approximately 60 months
Population: Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Duration of Response | NA months |
| Cohort B: Ponatinib 15 mg | Duration of Response | NA months |
| Cohort C: Nilotinib 400 mg | Duration of Response | NA months |
Secondary
Overall Survival
Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive.
Time frame: Up to end of study (approximately 60 months)
Population: Safety Population includes all participants who have received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Overall Survival | NA months |
| Cohort B: Ponatinib 15 mg | Overall Survival | NA months |
| Cohort C: Nilotinib 400 mg | Overall Survival | NA months |
Secondary
Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)
CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \<450 x 10\^9/L; No blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood \<5%; No extramedullary involvement (including no hepatomegaly or splenomegaly).
Time frame: 3 months after the first dose of study treatment
Population: Safety Population includes all participants who have received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | 60.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | 81.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Complete Cytogenetic Response (CCyR)
CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow.
Time frame: Up to 12 months
Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Complete Cytogenetic Response (CCyR) | 40.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Complete Cytogenetic Response (CCyR) | 55.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Complete Cytogenetic Response (CCyR) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Major Cytogenetic Response (MCyR)
MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization.
Time frame: Up to 12 months
Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Major Cytogenetic Response (MCyR) | 50.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Major Cytogenetic Response (MCyR) | 60.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Major Cytogenetic Response (MCyR) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Molecular Response (MR)
Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL\[IS\]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL\[IS\]), and MR4.5 (defined as ≤0.0032% BCR-ABL\[IS\]) after randomization.
Time frame: From Month 3 to every 3 months up to 48 months
Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. Number analyzed are participants with data available for analyses at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 48 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 3 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 24 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 45 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 24 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 21 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 42 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 27 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 48 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 39 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 30 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 27 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 36 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 33 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 45 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 33 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 36 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 30 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 30 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 39 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 15 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 27 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 42 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 42 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 24 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 21 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 45 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 33 | 30.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 15 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 48 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 12 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 12 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 3 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 39 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 9 | 0.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 6 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 36 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 6 | 60.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 36 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 39 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 12 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 33 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 42 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 15 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 30 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 45 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 3 | 70.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 27 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 48 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 9 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 24 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 3 | 30.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 18 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 21 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 6 | 30.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 18 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 18 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 9 | 30.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 6 | 20.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 15 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 12 | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 21 | 50.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 18 | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 9 | 50.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 27 | 19.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 12 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 27 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 48 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 3 | 38.1 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 6 | 57.1 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 9 | 52.4 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 12 | 52.4 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 15 | 52.4 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 18 | 47.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 21 | 52.4 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 24 | 47.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 30 | 38.1 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 33 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 36 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 39 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 42 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 45 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 48 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 3 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 6 | 28.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 9 | 28.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 12 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 39 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 15 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 21 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 24 | 19.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 27 | 42.9 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 30 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 33 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 36 | 19.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 39 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 42 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 45 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 48 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 3 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 6 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 9 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 18 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 21 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 24 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 30 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 33 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 36 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 42 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 45 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 15 | 28.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 18 | 38.1 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 21 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 24 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 27 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 30 | 33.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 33 | 28.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 36 | 28.6 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 39 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 42 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 45 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 48 | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 3 | 0.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 6 | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 9 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 12 | 9.5 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 15 | 19.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 18 | 23.8 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 24 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 48 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 42 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 21 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 21 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 45 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 39 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 48 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 12 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 9 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 18 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 15 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 6 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 3 | 0.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 18 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 3 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 18 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 21 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 48 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 15 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 24 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 45 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 6 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 27 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 42 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 15 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 30 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 39 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 6 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 33 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 36 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 9 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 36 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 33 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 12 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 39 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 30 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 6 | 0.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 3 | 0.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 3 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 9 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 48 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 12 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 45 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 42 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 18 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 42 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 27 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 21 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 15 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 12 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 24 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 39 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 27 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 36 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR3/MMR - Month 45 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 30 | 27.3 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 33 | 9.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 24 | 54.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 33 | 0.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 30 | 36.4 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR2 - Month 9 | 45.5 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4.5 - Month 36 | 18.2 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Molecular Response (MR) | MR4 - Month 27 | 36.4 percentage of participants |
Secondary
Percentage of Participants With MR1
MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months.
Time frame: Month 3
Population: Safety Population includes all participants who have received at least 1 dose of study drug, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With MR1 | 70.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With MR1 | 66.7 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With MR1 | 63.6 percentage of participants |
Secondary
Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML
Progression to AP is defined as: \>=15% and \<30% blasts in peripheral blood or bone marrow or \>=20% basophils in peripheral blood or bone marrow or \>=30% blasts + promyelocytes in peripheral blood or bone marrow (but \<30% blasts) or \<100\*10\^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: \>=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Time frame: Up to end of study (Up to approximately 60 months)
Population: As the study was terminated, data was not collected and analyzed for this outcome measure.
Secondary
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From first dose up to end of treatment (Up to approximately 45 months)
Population: Safety Population includes all participants who have received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Reduction | 40.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Treatment Discontinuation | 10.0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Interruption | 70.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Reduction | 19.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Treatment Discontinuation | 23.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Interruption | 38.1 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Treatment Discontinuation | 25.0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Interruption | 41.7 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | TEAEs Leading to Dose Reduction | 33.3 percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs)
TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event.
Time frame: From first dose up to 30 days post last dose (Up to approximately 46 months)
Population: Safety Population includes all participants who have received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-AOE | 0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-VOEs | 0 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | AEs | 100 percentage of participants |
| Cohort A: Ponatinib 30 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | SAEs | 40.0 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | SAEs | 14.3 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-AOE | 4.8 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | AEs | 95.2 percentage of participants |
| Cohort B: Ponatinib 15 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-VOEs | 0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | SAEs | 16.7 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-VOEs | 0 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | AEs | 100 percentage of participants |
| Cohort C: Nilotinib 400 mg | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-AOE | 8.3 percentage of participants |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment.
Time frame: Up to end of study (approximately 60 months)
Population: Safety Population includes all participants who have received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Progression-free Survival (PFS) | NA months |
| Cohort B: Ponatinib 15 mg | Progression-free Survival (PFS) | NA months |
| Cohort C: Nilotinib 400 mg | Progression-free Survival (PFS) | NA months |
Secondary
Time to Response
Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as \<=0.1% BCR-ABL.
Time frame: Up to approximately 60 months
Population: Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Time to Response | 3.07 months |
| Cohort B: Ponatinib 15 mg | Time to Response | 6.29 months |
| Cohort C: Nilotinib 400 mg | Time to Response | 6.07 months |