CompletedNCT01667133Updated Jun 13, 2022Results posted

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

A Phase 1/2 interventional study of ponatinib - Phase 1 and ponatinib - Phase 2 in Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL), sponsored by Ariad Pharmaceuticals. Completed at 11 sites in Japan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-13.

Sponsored by Ariad Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 35
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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).

Read the detailed description

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.

Conditions studied

Chronic Myeloid Leukemia (CML)
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Browse trials for

Keywords

Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 637 are open to participants now.

This study's enrollment of 35 is close to the median of 38 across 4,248 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Ariad Pharmaceuticals is the lead sponsor of 13 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, as follows:
- All patients must have screening bone marrow (BM) cytogenetics with conventional banding performed within 42 days prior to beginning treatment.
- Examination of at least 20 metaphases is required in patients in CP. If less than 20 metaphases are examined, the BM aspirate must be repeated.
- Adequate BM aspirate with differential cell counts is required in patients with AP, BP, or Ph+ ALL. If an adequate aspirate is not obtained, the aspirate must be repeated.
Be previously treated with and resistant, or intolerant, as defined in the protocol, to either dasatinib or nilotinib for CML or at least one TKI for Ph+ ALL, regardless of whether dasatinib or nilotinib or the prior TKI were used to treat newly diagnosed or resistant patients.
Must be ≥ 18 years old.
Provide written informed consent.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Minimum life expectancy of 3 months or more.
Adequate renal function defined as serum creatinine \< 1.5 × upper limit of normal (ULN) for institution.
Adequate hepatic function defined as:
1. Total bilirubin \< 1.5 × ULN
2. Alanine aminotransferase (ALT [SGPT]) and aspartate aminotransferase (AST [SGOT]) \< 2.5 × ULN for institution (\< 5 × ULN if liver involvement with leukemia)
3. Prothrombin time \< 1.5 × ULN
Normal pancreatic status defined as:
1. Lipase ≤ 1.5 × ULN for institution
2. Amylase ≤ 1.5 × ULN for institution
Normal QT interval corrected (Fridericia) (QTcF) interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
Female and male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study.
Ability to comply with study procedures, in the Investigator's opinion.

Exclusion criteria

Exclusion Criteria:

Patients are not eligible for participation in the study if they meet any of the following exclusion criteria:

Received TKI therapy within 7 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 [NCI CTCAE v.4.0]) from adverse events (AEs) (except alopecia) due to agents previously administered.
Received other therapies as follows:
1. For CP and AP patients, received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib.
2. For BP patients, received chemotherapy within 7 days prior to the first dose of ponatinib. Otherwise, 2a applies.
3. For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of ponatinib and other chemotherapy within 7 days prior to the first dose of ponatinib. Otherwise, 2a applies.
4. All patients are excluded if they have not recovered (> grade 1 by NCI CTCAE v.4.0) from AEs (except alopecia) due to agents previously administered.
Underwent autologous or allogeneic stem cell transplant \< 60 days prior to receiving the first dose of ponatinib; any evidence of ongoing graft versus-host disease (GVHD) or GVHD requiring immunosuppressive therapy.
Take medications that are known to be associated with Torsades de Pointes.
Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
Have previously been treated with ponatinib.
Patients with CP-CML are excluded if they are in CCyR.
Patients with CP-CML are excluded if a baseline BM aspirate adequate for conventional cytogenetic analysis with 20 metaphases examined is not available.
Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if they are in MaHR.
Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if a baseline BM aspirate adequate for cell count and differential report is not available. Patients with a fibrotic marrow or dry tap that does not yield adequate cell counts for diagnosis are not evaluable for classification, and endpoints are not eligible.
Have active central nervous system (CNS) disease as evidenced by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
Have significant or active cardiovascular disease, specifically including, but not restricted to:
1. Myocardial infarction within 3 months prior to first dose of ponatinib
2. History of clinically significant atrial arrhythmia or any ventricular arrhythmia
3. Unstable angina within 3 months prior to first dose of ponatinib
4. Congestive heart failure within 3 months prior to first dose of ponatinib
Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
Have a history of pancreatitis or alcohol abuse.
Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL).
Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.
Have been diagnosed with another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ, or controlled prostate cancer, which are allowed within 3 years).
Are pregnant or lactating. Women of childbearing potential must agree to an effective contraception from the time of signing the informed consent through the Follow-up Visit, approximately 30 days after last dose of ponatinib.
Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of ponatinib.
Have ongoing or active infection (including known history of human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]). Testing for these viruses is not required in the absence of history.
Suffer from any condition or illness that, in the opinion of the Investigator or the Medical Monitor, would compromise patients safety or interfere with the evaluation of the safety of the study drug.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 35 participants (actual)

Study arms

Experimental
Phase 1 dose escalation
Phase 1
Drug: ponatinib - Phase 1
Experimental
Phase 2 expansion
Phase 2
Drug: ponatinib - Phase 2

Interventions

Drugponatinib - Phase 1
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.
Also known as: AP24534
Drugponatinib - Phase 2
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.
Also known as: AP24534

What researchers measure

Primary outcomes

Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) as a Measure of Safety Profile to Determine Recommended Dose of Ponatinib
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.
Time frame: Cycle 1 (Cycle length= 28 days)
Phase 2, CP-CML Participants: Percentage of Participants With Major Cytogenetic Response (MCyR)
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.
Time frame: Baseline up to 60 months
Phase 2, BP-CML and Ph+ALL: Percentage of Participants With Major Hematologic Response (MaHR)
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.
Time frame: Baseline up to 60 months

Secondary outcomes

CP-CML Participants: Percentage of Participants With CHR
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).
Time frame: Baseline up to 60 months
CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Confirmed MCyR
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.
Time frame: Baseline up to 60 months
CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Major Molecular Response (MMR)
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 frame: Baseline up to 60 months
CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Median Time to Response (TTR)
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.
Time frame: From the first dose of study treatment until the criteria for response were first met (up to 60 months)
CP-CML and Advanced Phase Participants: Median Duration of Response (DOR)
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).
Time frame: From the first assessment at which criteria for response was met until the criteria for progression was first met (up to 60 months)
CP-CML and Advanced Phase Participants: Median Progression-free Survival (PFS)
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).
Time frame: From the first assessment at which criteria for response was met until the criteria for progression or death was met (up to 60 months)
CP-CML and Advanced Phase Participants: Overall Survival (OS)
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).
Time frame: From the first dose of study treatment until death (up to 60 months)
Cmax: Maximum Observed Plasma Concentration for Ponatinib
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Tmax: Time to Reach the Cmax for Ponatinib
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Ponatinib
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
T1/2: Terminal Phase Elimination Half-life for Ponatinib
Time frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)

Results

Posted Jun 13, 2022

Participant flow

Participants took part in the study at 9 investigative sites in Japan from 31 August 2012 to 02 August 2018.

Phase 1: Dose-escalation

Participant flow — Phase 1: Dose-escalation
Milestone	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL
Started	1	1	4	3	1	1	1
Completed	1	0	0	2	0	0	0
Not completed	0	1	4	1	1	1	1
Withdrew: Adverse event	0	0	1	0	0	0	0
Withdrew: Lack of efficacy	0	0	1	0	0	0	0
Withdrew: Progressive disease	0	1	2	0	1	1	1
Withdrew: Withdrawal by subject	0	0	0	1	0	0	0

Phase 2: Dose-expansion

Participant flow — Phase 2: Dose-expansion
Milestone	Ponatinib 15 mg: Phase 2 CP- CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
Started	2	1	11	3	6
Completed	0	0	5	0	0
Not completed	2	1	6	3	6
Withdrew: Adverse event	2	1	1	0	0
Withdrew: Lack of efficacy	0	0	2	0	0
Withdrew: Progressive disease	0	0	0	3	5
Withdrew: Withdrawal by subject	0	0	2	0	0
Withdrew: Death	0	0	1	0	0
Withdrew: Other	0	0	0	0	1

Outcome measures

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

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.

Time frame:: Cycle 1 (Cycle length= 28 days)
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) as a Measure of Safety Profile to Determine Recommended Dose of Ponatinib
Participants	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) as a Measure of Safety Profile to Determine Recommended Dose of Ponatinib	0	0	1	1	0	0	0

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

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.

Time frame:: Baseline up to 60 months
Reported as:: Number · percentage of participants

Phase 2, CP-CML Participants: Percentage of Participants With Major Cytogenetic Response (MCyR)
percentage of participants	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 CP-CML
Phase 2, CP-CML Participants: Percentage of Participants With Major Cytogenetic Response (MCyR)	50 (1.3 to 98.7)	63.6 (30.8 to 89.1)

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

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.

Time frame:: Baseline up to 60 months
Reported as:: Number · percentage of participants

Phase 2, BP-CML and Ph+ALL: Percentage of Participants With Major Hematologic Response (MaHR)
percentage of participants	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
Phase 2, BP-CML and Ph+ALL: Percentage of Participants With Major Hematologic Response (MaHR)	0 (0 to 97.5)	33.3 (0.8 to 90.6)	83.3 (35.9 to 99.6)

SecondaryCP-CML Participants: Percentage of Participants With CHR

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).

Time frame:: Baseline up to 60 months
Reported as:: Number · percentage of participants

CP-CML Participants: Percentage of Participants With CHR
percentage of participants	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 CP-CML
CP-CML Participants: Percentage of Participants With CHR	100 (2.5 to 100)	100 (29.2 to 100)	100 (15.8 to 100)	90.9 (58.7 to 99.8)

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

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.

Time frame:: Baseline up to 60 months
Reported as:: Number · percentage of participants

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Confirmed MCyR
percentage of participants	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Confirmed MCyR	100 (2.5 to 100)	0 (0.0 to 97.5)	0 (0 to 60.2)	100 (29.2 to 100)	100 (2.5 to 100)	100 (2.5 to 100)	100 (2.5 to 100)	0 (0.0 to 84.2)	0 (0.0 to 97.5)	63.6 (30.8 to 89.1)	33.3 (0.8 to 90.6)	16.7 (0.4 to 64.1)

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

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 frame:: Baseline up to 60 months
Reported as:: Number · percentage of participants

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Major Molecular Response (MMR)
percentage of participants	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Percentage of Participants With Major Molecular Response (MMR)	0 (0.0 to 97.5)	0 (0.0 to 97.5)	0 (0.0 to 60.2)	100 (29.2 to 100)	0 (0.0 to 97.5)	0 (0.0 to 97.5)	0 (0.0 to 97.5)	50.0 (1.3 to 98.7)	9 (0.0 to 97.5)	27.3 (6.0 to 61.0)	33.3 (0.8 to 90.6)	0 (0.0 to 45.9)

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

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.

Time frame:: From the first dose of study treatment until the criteria for response were first met (up to 60 months)
Reported as:: Median · days

CP-CML, AP-CML, BP-CML, and Ph+ALL Participants: Median Time to Response (TTR)
days	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
Cytogenic response	85.0 (85 to 85)	NA (NA to NA)	NA (NA to NA)	85 (85 to 169)	113 (113 to 113)	29 (29 to 29)	28 (28 to 28)	84 (84 to 84)	NA (NA to NA)	167 (84 to 755)	31 (31 to 31)	29 (24 to 58)
Hematologic response	NA (NA to NA)	22 (22 to 22)	14.5 (14 to 15)	NA (NA to NA)	56 (56 to 56)	15 (15 to 15)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	17 (17 to 17)	15 (10 to 44)
Molecular response	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	85 (85 to 421)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	84 (84 to 84)	NA (NA to NA)	253.0 (84 to 842)	58 (58 to 58)	NA (NA to NA)

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

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).

Time frame:: From the first assessment at which criteria for response was met until the criteria for progression was first met (up to 60 months)
Reported as:: Median · days

CP-CML and Advanced Phase Participants: Median Duration of Response (DOR)
days	Ponatinib 30 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 30 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With Other Mutations	Ponatinib 45 mg: Phase 2 Advanced Phase Participants With Other Mutations
Cytogenic response	1513.0 (NA to NA)	—	—	NA (NA to NA)	—	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	—	NA (NA to NA)	—	31.0 (20.0 to NA)	—	169.0 (NA to NA)	—	205.0 (NA to NA)
Hematologic response	NA (NA to NA)	—	—	NA (NA to NA)	—	NA (1226.0 to NA)	NA (NA to NA)	NA (85.0 to NA)	56.5 (38.0 to NA)	NA (NA to NA)	—	50.5 (33.0 to NA)	NA (NA to NA)	226.0 (NA to NA)	—	113.5 (110.0 to NA)
Molecular response	—	—	—	NA (NA to NA)	—	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	—	—	—	168.0 (NA to NA)	—	—	—	—

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

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).

Time frame:: From the first assessment at which criteria for response was met until the criteria for progression or death was met (up to 60 months)
Reported as:: Median · days

CP-CML and Advanced Phase Participants: Median Progression-free Survival (PFS)
days	Ponatinib 30 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 30 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With Other Mutations	Phase 2: Ponatinib 45 mg, Advanced Phase Participants With Other Mutations
CP-CML and Advanced Phase Participants: Median Progression-free Survival (PFS)	1597.0 (NA to NA)	—	—	NA (85.0 to NA)	—	NA (NA to NA)	NA (NA to NA)	NA (113.0 to NA)	51.0 (29.0 to NA)	320.0 (113.0 to NA)	33.0 (NA to NA)	100.0 (10.0 to NA)	56.5 (10.0 to NA)	281.0 (NA to NA)	—	127.5 (85.0 to NA)

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

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).

Time frame:: From the first dose of study treatment until death (up to 60 months)
Reported as:: Median · days

CP-CML and Advanced Phase Participants: Overall Survival (OS)
days	Ponatinib 30 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 1 CP-CML Participants With Other Mutations	Ponatinib 15 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 45 mg: Phase 2 CP-CML Participants With Other Mutations	Ponatinib 30 mg: Phase 1 Ponatinib 30 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With T315I Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 45 mg: Phase 2 Advanced Phase Participants With T315I Mutations	Ponatinib 30 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 45 mg: Phase 1 Advanced Phase Participants With Other Mutations	Ponatinib 15 mg: Phase 2 Advanced Phase Participants With Other Mutations	Ponatinib 45 mg: Phase 2 Advanced Phase Participants With Other Mutations
CP-CML and Advanced Phase Participants: Overall Survival (OS)	NA (NA to NA)	—	—	NA (NA to NA)	—	NA (NA to NA)	NA (NA to NA)	NA (1305.0 to NA)	201.0 (194.0 to NA)	NA (527.0 to NA)	109.0 (NA to NA)	264.0 (169.0 to NA)	131.0 (10.0 to NA)	382.0 (NA to NA)	—	550.5 (281.0 to NA)

SecondaryCmax: Maximum Observed Plasma Concentration for Ponatinib

Time frame:: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Reported as:: Mean · nanogram per milliliter (ng/mL)

Cmax: Maximum Observed Plasma Concentration for Ponatinib
nanogram per milliliter (ng/mL)	Ponatinib 15 mg	Ponatinib 30 mg	Ponatinib 45 mg
Cmax: Maximum Observed Plasma Concentration for Ponatinib	23.67 ± 7.136	31.55 ± 9.072	89.13 ± 24.63

SecondaryTmax: Time to Reach the Cmax for Ponatinib

Time frame:: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Reported as:: Median · hour

Tmax: Time to Reach the Cmax for Ponatinib
hour	Ponatinib 15 mg	Ponatinib 30 mg	Ponatinib 45 mg
Tmax: Time to Reach the Cmax for Ponatinib	4.00 (4.0 to 6.2)	6.75 (3.9 to 8.1)	5.00 (4.0 to 6.0)

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

Time frame:: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Reported as:: Mean · hour*nanogram per milliliter (h*ng/mL)

AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Ponatinib
hournanogram per milliliter (hng/mL)	Ponatinib 15 mg	Ponatinib 30 mg	Ponatinib 45 mg
AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Ponatinib	336.00 ± 129.55	495.98 ± 154.09	1385.5 ± 456.20

SecondaryT1/2: Terminal Phase Elimination Half-life for Ponatinib

Time frame:: Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days)
Reported as:: Median · hours

T1/2: Terminal Phase Elimination Half-life for Ponatinib
hours	Ponatinib 15 mg	Ponatinib 30 mg	Ponatinib 45 mg
T1/2: Terminal Phase Elimination Half-life for Ponatinib	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)

Adverse events

Collected over Treatment-emergent adverse events (TEAEs) are AEs that started after the first dose of study drug up to 5 years and 11 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Ponatinib 30 mg: Phase 1 CP-CML	0/1 (0%)	1/1 (100%)	1/1 (100%)
Ponatinib 30 mg: Phase 1 AP-CML	0/1 (0%)	0/1 (0%)	1/1 (100%)
Ponatinib 30 mg: Phase 1 Ph+ ALL	4/4 (100%)	2/4 (50%)	3/4 (75%)
Ponatinib 45 mg: Phase 1 CP-CML	0/3 (0%)	2/3 (66.7%)	3/3 (100%)
Ponatinib 45 mg: Phase 1 AP-CML	1/1 (100%)	1/1 (100%)	1/1 (100%)
Ponatinib 45 mg: Phase 1 BP-CML	0/1 (0%)	0/1 (0%)	1/1 (100%)
Ponatinib 45 mg: Phase 1 Ph+ ALL	1/1 (100%)	0/1 (0%)	1/1 (100%)
Ponatinib 15 mg: Phase 2 CP-CML	0/2 (0%)	1/2 (50%)	2/2 (100%)
Ponatinib 15 mg: Phase 2 Ph+ ALL	1/1 (100%)	1/1 (100%)	1/1 (100%)
Ponatinib 45 mg: Phase 2 CP-CML	1/11 (9.1%)	6/11 (54.5%)	11/11 (100%)
Ponatinib 45 mg: Phase 2 BP-CML	3/3 (100%)	2/3 (66.7%)	3/3 (100%)
Ponatinib 45 mg: Phase 2 PH+ ALL	6/6 (100%)	1/6 (16.7%)	6/6 (100%)

Most frequent serious events

Showing 10 of 39

Most frequent serious events
Event	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
Myocardial InfarctionCardiac disorders	0/1	0/1	0/4	0/3	1/1	0/1	0/1	0/2	0/1	2/11	0/3	0/6
Angina unstableCardiac disorders	0/1	0/1	0/4	0/3	1/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/1	0/1	0/4	0/3	1/1	0/1	0/1	0/2	0/1	0/11	1/3	0/6
Febrile neutropeniaBlood and lymphatic system disorders	0/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	1/1	0/11	0/3	0/6
Acute kidney injuryRenal and urinary disorders	0/1	0/1	1/4	0/3	1/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
Diverticulum intestinalGastrointestinal disorders	1/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
IleusGastrointestinal disorders	1/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
PneumoniaInfections and infestations	1/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
Mechanical ileusGastrointestinal disorders	1/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	0/1	0/11	0/3	0/6
Laryngeal squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/1	0/1	0/4	0/3	0/1	0/1	0/1	1/2	0/1	0/11	0/3	0/6

Most frequent other events

Showing 10 of 231

Most frequent other events
Event	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL
Platelet count decreasedInvestigations	0/1	0/1	1/4	1/3	1/1	0/1	0/1	1/2	0/1	7/11	0/3	2/6
Lipase increasedInvestigations	1/1	0/1	1/4	1/3	0/1	1/1	0/1	0/2	0/1	3/11	1/3	3/6
Gamma-glutamyltransferase increasedInvestigations	1/1	0/1	2/4	1/3	0/1	0/1	1/1	0/2	0/1	1/11	1/3	3/6
Alanine aminotransferase increasedInvestigations	1/1	0/1	2/4	1/3	0/1	0/1	0/1	2/2	0/1	0/11	1/3	2/6
Aspartate aminotransferase increasedInvestigations	1/1	0/1	2/4	1/3	0/1	0/1	0/1	2/2	0/1	0/11	1/3	2/6
Blood alkaline phosphatase increasedInvestigations	1/1	0/1	1/4	1/3	0/1	0/1	1/1	1/2	0/1	0/11	0/3	1/6
Neutrophil count decreasedInvestigations	0/1	0/1	1/4	0/3	0/1	1/1	1/1	1/2	0/1	4/11	2/3	2/6
White blood cell count decreasedInvestigations	0/1	0/1	1/4	0/3	1/1	1/1	0/1	0/2	0/1	0/11	0/3	1/6
Blood creatinine increasedInvestigations	1/1	0/1	0/4	0/3	0/1	0/1	0/1	0/2	0/1	1/11	0/3	1/6
Lymphocyte count decreasedInvestigations	0/1	0/1	0/4	0/3	1/1	0/1	0/1	0/2	0/1	2/11	0/3	0/6

Baseline characteristics

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

Age, Continuous
Age, Continuous(years)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Mean	61.0	62.0	56.5 ± 11.73	60.7 ± 12.86	57.0	58.0	30.0	61.5 ± 14.85	76.0	59.1 ± 13.78	67.7 ± 4.04	58.3 ± 13.78	59.4 ± 12.44

Sex: Female, Male
Sex: Female, Male(Participants)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Female	0	1	2	0	0	1	0	0	0	6	1	4	15
Male	1	0	2	3	1	0	1	2	1	5	2	2	20

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Asian	1	1	4	3	1	1	1	2	1	11	3	6	35

Region of Enrollment
Region of Enrollment(Participants)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Japan	1	1	4	3	1	1	1	2	1	11	3	6	35

Weight
Weight(kilogram (kg))	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Mean	67.0	57.0	45.8 ± 3.93	74.1 ± 6.49	55.8	60.0	54.6	60.0 ± 8.49	60.5	59.0 ± 9.93	54.0 ± 10.99	53.7 ± 11.84	57.5 ± 10.54

Height
Height(centimeter (cm))	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
Mean	163.6	155.9	165.1 ± 8.89	172.4 ± 6.61	170.5	156.4	170.7	169.5 ± 2.83	166.0	159.5 ± 10.15	162.4 ± 6.92	158.0 ± 8.95	162.5 ± 8.95

Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 BP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
0 = Fully Active	1	1	2	3	0	1	0	2	0	11	1	6	28
1 = Restricted in Physical Activity; Ambulatory	0	0	2	0	1	0	1	0	1	0	2	0	7

Participants with Initial Diagnosis of Leukemia
Participants with Initial Diagnosis of Leukemia(Participants)	Ponatinib 30 mg: Phase 1 CP-CML	Ponatinib 30 mg: Phase 1 AP-CML	Ponatinib 30 mg: Phase 1 Ph+ ALL	Ponatinib 45 mg: Phase 1 CP-CML	Ponatinib 45 mg: Phase 1 AP-CML	Ponatinib 45 mg: Phase 1 Ph+ ALL	Ponatinib 15 mg: Phase 2 CP-CML	Ponatinib 15 mg: Phase 2 Ph+ ALL	Ponatinib 45 mg: Phase 2 CP-CML	Ponatinib 45 mg: Phase 2 BP-CML	Ponatinib 45 mg: Phase 2 PH+ ALL	Total
CP-CML	1	1	0	3	1	0	2	0	11	1	0	20
AP-CML	0	0	0	0	0	0	0	0	0	1	0	1
BP-CML	0	0	0	0	1	0	0	0	0	1	0	2
Ph+ ALL	0	0	4	0	0	1	0	1	0	0	6	12

3 further baseline measures are reported on the registry.

Study locations

11 sites

Aichi Cancer Center Hospital
Nagoya-shi, Aichi 464-8681, Japan
Akita University Hospital
Akita-shi, Akita 010-8543, Japan
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
Hiroshima-shi, Hiroshima 730-8619, Japan
Kyushu University Hospital
Hukuoka-shi, Hukuoka, Japan
Kinki University Hospital, Faculty of Medicine
Osakasayama-shi, Osaka 589-8511, Japan
The Cancer Institute Hospital Japanese Foundation for Cancer Research
Koto, Tokyo, Japan
The University of Tokyo, The Institute of Medical Science
Minato-ku, Tokyo, Japan
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
Osaka City University Hospital
Shinjuku-ku, Tokyo, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
Tokyo Medical University Hospital
Shinjuku-ku, Tokyo, Japan

References and documents

Publications

Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development. J Clin Pharmacol. 2022 Apr;62(4):555-567. doi: 10.1002/jcph.1990. Epub 2021 Dec 16. PubMed 34699069 ↗
Tojo A, Kyo T, Yamamoto K, Nakamae H, Takahashi N, Kobayashi Y, Tauchi T, Okamoto S, Miyamura K, Hatake K, Iwasaki H, Matsumura I, Usui N, Naoe T, Tugnait M, Narasimhan NI, Lustgarten S, Farin H, Haluska F, Ohyashiki K. Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study. Int J Hematol. 2017 Sep;106(3):385-397. doi: 10.1007/s12185-017-2238-9. Epub 2017 Apr 25. PubMed 28444644 ↗

Study documents

Study protocol · Nov 21, 2013
Statistical analysis plan · Mar 4, 2015

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Icf, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 13, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01667133
Lead sponsor: Ariad Pharmaceuticals
Responsible party: Sponsor
First posted: Aug 17, 2012
Start date: Aug 31, 2012
Primary completion: Aug 2, 2018
Completion: Aug 2, 2018
Results posted: Jun 13, 2022
Last update: Jun 13, 2022

Study contacts

Medical Director

study director · Takeda

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Leukemia→

Other studies from this sponsor

Ariad Pharmaceuticals

Start the discussion