Overview

This trial is active, not recruiting.

Conditions chronic myeloid leukemia (cml), ph+ acute lymphoblastic leukemia (all)
Treatment ponatinib 45 mg qd
Phase phase 2
Sponsor Ariad Pharmaceuticals
Start date September 2010
End date May 2016
Trial size 449 participants
Trial identifier NCT01207440, 2010-020414-28, AP24534-10-201

Summary

The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with Ph positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the T315I mutation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Chronic Phase (CP) CML resistant or intolerant (R/I) to dasatinib or nilotinib
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)
(Experimental)
Accelerated Phase (AP) CML resistant or intolerant (R/I) to dasatinib or nilotinib
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)
(Experimental)
Blast Phase (BP) CML or Ph+ ALL resistant or intolerant (R/I) to dasatinib or nilotinib or Ph+ ALL resistant or intolerant (R/I) to dasatinib or nilotinib
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)
(Experimental)
CP-CML patients who have the T315I mutation of BCR-ABL
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)
(Experimental)
AP-CML patients who have the T315I mutation of BCR-ABL
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)
(Experimental)
BP-CML or Ph+ ALL patients who have the T315I mutation of BCR-ABL
ponatinib 45 mg qd AP24534
45 mg tablet taken orally once daily (QD)

Primary Outcomes

Measure
Major cytogenetic response (MCyR) CP patients, and Major Hematologic Response (MaHR) AP/BP and Ph+ ALL patients
time frame: up to 24 months after first dose

Secondary Outcomes

Measure
Clinical response, molecular response, clinical outcomes and safety
time frame: up to 24 months after first dose

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL - Previously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any TKI therapy including imatinib - ≥18 years old - ECOG performance status ≤2 - Normal pancreatic function - Normal QTcF interval ≤450 ms for males and ≤470 ms for females - Adequate renal and hepatic function - Minimum life expectancy of ≥3 months - Provide written informed consent - Negative pregnancy test and agree to use effective form of contraception (as applicable) - Ability to comply with study procedures, in the Investigator's opinion. Exclusion Criteria: - Received prior tyrosine kinase inhibitor (TKI) treatment within 7 days prior to receiving the first dose of ponatinib, or have not recovered from adverse events (except alopecia) due to agents previously administered. - Received other therapies as follows: 1. For CML chronic phase (CP) and accelerated phase (AP) patients, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib. 2. For CML blast phase (BP) patients, received chemotherapy within 14 days prior to the first dose of ponatinib. 3. For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of ponatinib; or vincristine within 7 days prior to the first dose of ponatinib; or received other chemotherapy within 14 days prior to the first dose of ponatinib. - Taking medications that are known to be associated with torsades de pointes - Previously treated with ponatinib - Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib - Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy - Require concurrent treatment with immunosuppressive agents - Have active Central Nervous System (CNS) disease - Have significant or active cardiovascular disease - 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) - Underwent major surgery within 14 days prior to first dose of ponatinib - Have ongoing or active infection - Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib - Diagnosed with another primary malignancy in the past 3 years - Pregnant or lactating - Suffer from any other condition or illness that would compromise safety

Additional Information

Official title A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia
Description The preliminary analysis of the phase 1 clinical trial revealed evidence of clinical antitumor activity in patients with resistance to approved second-generation tyrosine kinase inhibitors (TKI), dasatinib and nilotinib, including patients with the T315I mutation of BCR-ABL. This study, taken together with the strong preclinical data that characterize ponatinib, provides the rationale for moving to a pivotal phase 2 trial of this agent in a population of patients with chronic myeloid leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) who are resistant or intolerant to prior TKI therapy and in those patients with the T315I mutation.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Ariad Pharmaceuticals.