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

COMPLETEDPHASE1/PHASE2

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)

NCT01667133•Ariad Pharmaceuticals

View on ClinicalTrials.gov

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).

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. 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.
•2. 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.
•3. Must be ≥ 18 years old.
•4. Provide written informed consent.
•5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
•6. Minimum life expectancy of 3 months or more.
•7. Adequate renal function defined as serum creatinine \< 1.5 × upper limit of normal (ULN) for institution.
+11 more criteria

Exclusion Criteria

•1. 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.
•2. 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.
•3. 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.
•4. Take medications that are known to be associated with Torsades de Pointes.
•5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
•6. Have previously been treated with ponatinib.
+18 more criteria

Locations (11)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Akita University Hospital

Akita, Akita, Japan

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, Hiroshima, Japan

Kyushu University Hospital

Hukuoka-shi, Hukuoka, Japan

Kinki University Hospital, Faculty of Medicine

Osakasayama-shi, Osaka, 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

Key Dates

Start Date

August 31, 2012

Primary Completion Date

August 2, 2018

Completion Date

August 2, 2018

Last Updated

June 13, 2022

Enrollment

ACTUAL participants

Conditions

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

Interventions

ponatinib - Phase 1

DRUG

ponatinib - Phase 2

DRUG

Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

NCT02790515

Acute Lymphoblastic Leukemia (ALL)Acute Myeloid Leukemia (AML)+5 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 13, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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