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Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will receive ponatinib 45 mg orally as a single dose once daily with or without food. Each patient will receive daily ponatinib until disease progression, unacceptable toxicity, or withdrawal of consent

ponatinib

This protocol will allow expanded access of ponatinib to patients ≥18 years with chronic myeloid leukemia (CML) any phase or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) who have failed all available treatment options.

This protocol will allow expanded access of ponatinib to patients ≥18 years with CML or Ph+ALL who have failed all available treatment options. Patients with chronic (CP) or accelerated phase (AP) CML must be previously treated with and resistant or intolerant to imatinib, dasatinib and nilotinib or develop the T315I mutation after any tyrosine kinase inhibitor (TKI) therapy. Patients with blast phase (BP) CML and Ph+ ALL must be previously treated with and resistant or intolerant to imatinib and dasatinib or develop the T315I mutation after any TKI therapy. No formal analysis will be performed on any data obtained. Safety information will be collected and adverse events will be tabulated for reporting purposes only.

Expanded Access Program of Ponatinib

Expanded Access Program of Ponatinib (AP24534) for Patients With Refractory Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia

Ariad Pharmaceuticals

Nilotinib

Dasatinib

30 mg dose of ponatinib taken orally once daily for at least the first 6 patients. If no dose-limiting toxicities are observed, the next patients will receive 45 mg dose of ponatinib taken orally once daily. Once the recommended dose is confirmed, all patients may receive the recommended dose, at the investigators' discretion.

ponatinib - Phase 1

Recommended dose of ponatinib as determined in the dose escalation phase. In addition, 3 patients will receive 15 mg dose once daily for 8 days for PK testing. These PK patients may be allowed to receive the recommended dose after PK testing is complete, at the investigators' discretion.

ponatinib - Phase 2

Medical Director

The purpose of this study is to assess the safety and efficacy of ponatinib in Japanese patients with chronic myeloid leukemia (CML) who have experienced failure of dasatinib or nilotinib or with Ph+ acute lymphoblastic leukemia (ALL) following failure of prior tyrosine kinase inhibitors (TKIs).

This multi-center, phase 1/2, open-label study will consist of two phases. The first will be a dose escalation phase employing a modified 3+3 design with two dose cohorts (30mg and 45mg). After 6 patients complete the first cycle in a cohort, safety events will be evaluated before opening the next dose cohort. Patients will continue on treatment as long as it is tolerated and disease progression has not occurred. Phase 2 will occur at the recommended dose determined in phase 1 in an additional 25 patients. Another 3 patients will be dosed at 15mg for collection of pharmacokinetic data. These patients may also escalate to the recommended dose and be assessed for efficacy and safety as phase 2 patients.

Efficacy measures include molecular, cytogenetic, and hematologic response rates at various time points; time to response; duration of response; and survival follow-up. Safety measures include routine physical and laboratory evaluations, adverse event monitoring, and ECGs. Other measures include mutation testing and molecular genetic assessment. Accrual is expected to take approximately 12 months, and patients will be followed for survival for up to 60 months from the last dose of study drug; therefore, the estimated duration of the trial is 72 months.

A Study of Ponatinib in Japanese Participants With Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL)

A Phase 1/2 Multi-center, Open-label Study of Ponatinib in Japanese Patients With Chronic Myeloid Leukemia (CML) Who Have Failed Dasatinib or Nilotinib or Ph+ Acute Lymphoblastic Leukemia (ALL) Who Have Failed Prior Tyrosine Kinase Inhibitors (TKIs)

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

DLT was evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 and was defined as any of the following events: 1. Grade greater than or equal to (\>=) 3 non-hematologic, with the exception of medically controllable toxicities (example; nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \<=3 days, but excluding alopecia; 2. Missed doses: \>25% of planned ponatinib doses over 28 days due to AEs in the first cycle; 3. Febrile neutropenia (the occurrence of an ANC \<500/microliter concurrently with a temperature elevation of \>101 degree Fahrenheit), when neutropenia is not related to underlying acute leukemia, as defined hematologic toxicity: Dose-limiting hematologic toxicity is the occurrence of a Grade 4 cytopenia \>28 days, not related to underlying disease according to the investigator. Bone marrow examination must demonstrate \<5% cellularity.

MCyR was defined as percentage of participants who achieved a complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) after the initiation of study treatment. Cytogenic response was the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow. CCyR: no Ph+ cells. PCyR: 1% to 35% Ph+ cells. Participants entering the study already in PCyR had to achieve a CCyR in order to be considered a success for the confirmed MCyR rate.

MaHR was defined as percentage of participants with complete hematologic response (CHR) or no evidence of leukemia (NEL). MaHR response was confirmed by a peripheral blood complete blood count (CBC) and differential no earlier than 28 days after the response was observed. Response criteria for CHR was reported as white blood cells (WBC)\<=institutional upper limit of normal (ULN), absolute neutrophil count (ANC)\>=1000/mm\^3, platelets\>=100,000/mm\^3, no blasts or promyelocytes in peripheral blood, BM blasts \<=5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement; Response criteria for NEL reported as WBC\<=institutional ULN, no blasts or promyelocytes in peripheral blood, BM blasts \<=5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement, at least 1 of the following: (i) 20,000/mm\^3\<=platelets\<100,000/mm\^3; (ii) 500/mm\^3\<=ANC\<1000/mm\^3.

Hematologic response was defined as CHR for CP-CML participants. Participants who entered the trial in CHR and continued to meet the criteria for CHR on study were analyzed as responders. Response criteria for CHR was reported as WBC \<=institutional ULN, platelets \<450,000 per cubic millimeter (/mm\^3), 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).

Confirmed MCyR was defined as 2 assessments of CCyR or PCyR at least 28 days apart. Participants entering the trial in PCyR must achieve two consecutive assessments of CCyR no fewer than 28 days apart in order to be considered as meeting the criteria for confirmed MCyR. Participants entering the trial in less than PCyR must achieve two consecutive assessments of PCyR or CCyR no fewer than 28 days apart in order to be considered as meeting the criteria for confirmed MCyR. CCyR: no Ph+ cells. PCyR: 1% to 35% Ph+ cells.

MMR was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL \<=0.1% on the International scale (equivalent to a 3-log reduction in transcript). Participants were non-responders in any of the following situations: BCR-ABL or ABL levels not detectable at baseline, no valid baseline or post-baseline assessment, and baseline assessment for e1a2 variant only.

Time to response was defined as the interval from the first dose of study treatment until the criteria for response were first met, censored at the last assessment of response. Median time to response was estimated by Kaplan-Meier method.

DOR: interval between first assessment at which criteria for response was met, until criteria for progression was met, censored at last date at which criteria for response was met. DOR was estimated using the Kaplan-Meier method. Progression criteria for CP was: death, development of AP/BP, or loss of CHR (in absence of cytogenic response), or loss of MCyR, or increasing WBC in participant without CHR (doubling of WBCs to \>20,000 on 2 occasions at least 4 weeks apart, after first week of therapy), as confirmed by development in complete blood cells (CBCs) at least 4 weeks apart; AP was: death, development of confirmed BP, loss of previous major/minor hematologic response over-2 week period, or no decrease from baseline levels in percentage blasts in peripheral blood/BM on all assessments over a 4-week period; and BP/Ph+ALL was: death/increasing blasts in peripheral blood or BM over a 4-week period. As planned, DOR is reported for all participants by entry mutation (T315I and Other).

PFS: interval from the first dose of study treatment until the criteria for progression or death were met, censored at the last response assessment. PFS was estimated using the Kaplan-Meier method. Progression criteria for CP was: death, development of AP/BP, or loss of CHR (in absence of cytogenic response), or loss of MCyR, or increasing WBC in participant without CHR (doubling of WBCs to \>20,000 on 2 occasions at least 4 weeks apart, after first week of therapy), as confirmed by development in CBCs at least 4 weeks apart; AP was: death, development of confirmed BP, loss of previous major/minor hematologic response over-2 week period, or no decrease from baseline levels in percentage blasts in peripheral blood/BM on all assessments over a 4-week period; BP/Ph+ALL was: death or increasing blasts in peripheral blood or BM over a 4-week period. As planned, PFS is reported for all participants by entry mutation (T315I and Other).

OS was defined as the interval from the first dose of study treatment until death, censored at the last date at which participant was known to be alive. Overall survival was estimated using the Kaplan-Meier method. As planned, OS is reported for all participants by entry mutation (T315I and Other).

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 CP-CML

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 AP-CML

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with Ph+ ALL resistant or intolerant to prior TKIs in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 Ph+ ALL

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 CP-CML

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle 1 for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 AP-CML

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with BP-CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 BP-CML

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with Ph+ ALL resistant or intolerant to prior TKIs in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 Ph+ ALL

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with CP-CML resistant or intolerant to dasatinib or nilotinib in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 15 mg: Phase 2 CP-CML

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with Ph+ ALL resistant or intolerant to prior TKIs in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment cycle 1 for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 15 mg: Phase 2 Ph+ ALL

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 CP-CML

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with BP-CML resistant or intolerant to dasatinib or nilotinib in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 BP-CML

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with PH+ ALL resistant or intolerant to prior TKI in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 PH+ ALL

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with CP-CML resistant or intolerant to dasatinib or nilotinib in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment Cycle for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with Ph+ ALL resistant or intolerant to prior TKIs in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment Cycle 1 for up to unacceptable drug reaction or disease progression (up to 60 months).

Total

Age, Continuous

Sex: Female, Male

Asian

Race/Ethnicity, Customized

Japan

Region of Enrollment

Weight

Height

0 = Fully Active

1 = Restricted in Physical Activity; Ambulatory

ECOG performance status used by doctors/researchers to assess how participant's disease is progressing, assess how disease affects daily living activities of participant and determine appropriate treatment/prognosis on 5-point scale. 0=Actively able to do activities; 1=Restricted in physical activity, able to do light/sedentary work; 2=Ambulatory (\>50% of waking hours), capable of self-care, unable to do any work activities; 3=Capable of limited self-care, confined to bed \>50% of waking hours; 4=Completely disabled, cannot do any self-care, totally confined to bed; 5=dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

CP-CML

AP-CML

BP-CML

Ph+ ALL

Participants with Initial Diagnosis of Leukemia

Time Since Diagnosis to Date of First Dose

Hepatomegaly

Splenomegaly

No extramedullary involvement

Participants with extramedullary disease sites were assessed. Extramedullary disease occurs when myeloma cells form tumors outside the bone marrow in the soft tissues or organs of the body.

Participants with Extramedullary Involvement

Greater than (>)0.1 - less than or equal to (<=)1%

>1 to <=10 percent (%)

>10%

e1a2 variant

Breakpoint cluster region-Abelson complex (BCR-ABL1) is an abnormal gene found in CML and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins. BCR-ABL ratio is assessed in % international scale (IS).

Participants with BCR-ABL Ratio

Treated population included all participants who had received at least 1 dose of study drug.

Ponatinib 45 mg: Phase 1 AP CML

DLT evaluable population (Phase 1 only) included all participants who had completed at least 75% of their planned doses during Cycle 1, unless missed doses were due to adverse events (AEs).

Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) as a Measure of Safety Profile to Determine Recommended Dose of Ponatinib

Treated population included all participants who had received at least 1 dose of study drug. This outcome measure was planned to be assessed only in CP-CML participants of Phase 2.

Phase 2, CP-CML Participants: Percentage of Participants With Major Cytogenetic Response (MCyR)

Treated population included all participants who had received at least 1 dose of study drug. This outcome measure was planned to be assessed only in BP-CML and Ph+ALL participants of Phase 2.

Phase 2, BP-CML and Ph+ALL: Percentage of Participants With Major Hematologic Response (MaHR)

Treated population included all participants who had received at least 1 dose of study drug. This outcome measure was planned to be assessed only in CP-CML Participants of Phase 1 and 2.

CP-CML Participants: Percentage of Participants With CHR

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle 1 in participant with Ph+ ALL resistant or intolerant to prior TKIs in Dose-escalation Phase 1.

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 6 months) in participants with BP-CML resistant or intolerant to dasatinib or nilotinib in Expansion Phase 2.

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Confirmed MCyR

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Major Molecular Response (MMR)

Cytogenic response

Hematologic response

Molecular response

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Median Time to Response (TTR)

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had (T)hreonine-315-(I)soleucine mutation (T315I) mutation of BCR-ABL in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 CP-CML Participants With T315I Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had T315I mutation of BCR-ABL in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 CP-CML Participants With T315I Mutations

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had T315I mutation of BCR-ABL in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment Cycle for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 15 mg: Phase 2 CP-CML Participants With T315I Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had T315I mutation of BCR-ABL in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 CP-CML Participants With T315I Mutations

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants CP-CML resistant or intolerant to dasatinib or nilotinib and who had mutation other than T315I, no mutations, and no sequencing data in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 CP-CML Participants With Other Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had mutation other than T315I, no mutations, and no sequencing data in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 CP-CML Participants With Other Mutations

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had mutation other than T315I, no mutations, and no sequencing data in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 15 mg: Phase 2 CP-CML Participants With Other Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had mutation other than T315I, no mutations, and no sequencing data in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 CP-CML Participants With Other Mutations

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had T315I mutation of BCR-ABL in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 Advanced Phase Participants With T315I Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had T315I mutation of BCR-ABL in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 Advanced Phase Participants With T315I Mutations

Ponatinib 15 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had T315I mutation of BCR-ABL in Expansion Phase 2.

Ponatinib 15 mg: Phase 2 Advanced Phase Participants With T315I Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had T315I mutation of BCR-ABL in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 Advanced Phase Participants With T315I Mutations

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had mutation other than T315I, no mutations, and no sequencing data in Dose-escalation Phase 1.

Ponatinib 30 mg: Phase 1 Advanced Phase Participants With Other Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had mutation other than T315I, no mutations, and no sequencing data in Dose-escalation Phase 1.

Ponatinib 45 mg: Phase 1 Advanced Phase Participants With Other Mutations

Ponatinib 15 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had mutation other than T315I, no mutations, and no sequencing data in Expansion Phase 2.

Ponatinib 15 mg: Phase 2 Advanced Phase Participants With Other Mutations

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had mutation other than T315I, no mutations, and no sequencing data in Expansion Phase 2.

Ponatinib 45 mg: Phase 2 Advanced Phase Participants With Other Mutations

Treated population by entry mutation. Here number analyzed "n" are the participants who were evaluable for this outcome measure for given categories.

CP-CML and Advanced Phase Participants: Median Duration of Response (DOR)

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had T315I mutation of BCR-ABL in Dose-escalation Phase 1.

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment cycle in participants with CP-CML resistant or intolerant to dasatinib or nilotinib and who had T315I mutation of BCR-ABL in Expansion Phase 2. Dose was increased to ponatinib 45 mg in the same participants at the discretion of Investigator and was administered as tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months).

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment Cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with AP-CML and BP-CML resistant or intolerant to dasatinib or nilotinib and Ph+ ALL participants and who had mutation other than T315I, no mutations, and no sequencing data in Expansion Phase 2.

Phase 2: Ponatinib 45 mg, Advanced Phase Participants With Other Mutations

Treated population by entry mutation. Here overall number analyzed "N" are the participants who were evaluable for this outcome measure.

CP-CML and Advanced Phase Participants: Median Progression-free Survival (PFS)

Ponatinib 30 mg: Phase 1 Ponatinib 30 mg: Phase 1 Advanced Phase Participants With T315I Mutations

CP-CML and Advanced Phase Participants: Overall Survival (OS)

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment Cycle 1 before 15 mg was dose-escalated to recommended phase 2 dose (RP2D) in participants with CP-CML, BP-CML, or AP-CML who were resistant or intolerant to dasatinib or nilotinib, or with Ph+ALL who were resistant or intolerant to prior TKIs.

Ponatinib 15 mg

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment Cycle 1 in participants with CP-CML, BP-CML, or AP-CML who were resistant or intolerant to dasatinib or nilotinib, or with Ph+ALL who were resistant or intolerant to prior TKIs.

Ponatinib 30 mg

Ponatinib 45 mg, tablet, orally, once daily in a 28-day treatment Cycle 1 in participants with CP-CML, BP-CML, or AP-CML who were resistant or intolerant to dasatinib or nilotinib, or with Ph+ALL who were resistant or intolerant to prior TKIs.

Ponatinib 45 mg

Treated population include all participants who had received at least 1 dose of study drug and for whom PK samples were collected. As planned, PK samples were analyzed per dose level.

Cmax: Maximum Observed Plasma Concentration for Ponatinib

Ponatinib 15 mg, tablet, orally, once daily for 7-days in a 28-day treatment Cycle 1 before 15 mg was dose-escalated to RP2D in participants with CP-CML, BP-CML, or AP-CML who were resistant or intolerant to dasatinib or nilotinib, or with Ph+ALL who were resistant or intolerant to prior TKIs.

Tmax: Time to Reach the Cmax for Ponatinib

AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Ponatinib

T1/2: Terminal Phase Elimination Half-life for Ponatinib

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with chronic phase (CP)-chronic myeloid leukemia (CML) resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with accelerated phase (AP)- CML resistant or intolerant to dasatinib or nilotinib in Dose-escalation Phase 1.

Ponatinib 30 mg, tablet, orally, once daily in a 28-day treatment cycle for up to unacceptable drug reaction or disease progression (up to 60 months) in participants with Philadelphia chromosome plus acute lymphoblastic leukemia (Ph+ ALL) resistant or intolerant to prior tyrosine kinase inhibitor (TKIs) in Dose-escalation Phase 1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Expanded Access Program of Ponatinib	NCT01592136	Chronic Myeloid... Philadelphia Ch...	ponatinib	18 Years -	Takeda
A Study of Ponatinib in Japanese Participants With Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01667133	Chronic Myeloid... Philadelphia Ch...	ponatinib - Pha... ponatinib - Pha...	18 Years -	Takeda
A Study of Ponatinib in Japanese Participants With Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01667133	Chronic Myeloid... Philadelphia Ch...	ponatinib - Pha... ponatinib - Pha...	18 Years -	Takeda
Expanded Access Program of Ponatinib	NCT01592136	Chronic Myeloid... Philadelphia Ch...	ponatinib	18 Years -	Takeda

Spots Global Cancer Trial Database for philadelphia chromosome positive acute lymphoblastic leukemia (ph+ all)