PONATINIB for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL) (PACE)
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.
Chronic Myeloid Leukemia (CML)
Ph+ Acute Lymphoblastic Leukemia (ALL)
Drug: Ponatinib (AP24534)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia|
- 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 ] [ Designated as safety issue: No ]
- For CML patients in CP at study entry: major cytogenetic response (MCyR), defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CP patients in CCyR are not eligible for this study.
- For CML patients in AP at study entry: major hematologic response (MaHR), defined as complete hematologic response (CHR) or no evidence of leukemia (NEL). AP patients in MaHR are not eligible for this study.
- For CML patients in BP at study entry or Ph+ ALL patients: MaHR, consisting of CHR or NEL. BP and Ph+ ALL patients in MaHR are not eligible for this study.
- Clinical response, molecular response, clinical outcomes and safety [ Time Frame: up to 24 months after first dose ] [ Designated as safety issue: No ]
For CML patients in CP:
- Hematologic responses: CHR;
- Cytogenetic responses: confirmed MCyR; and
- Molecular responses: major molecular response (MMR).
For CML patients in AP or BP or Ph+ ALL patients:
- Cytogenetic responses: CCyR, PCyR, confirmed MCyR; and
- Molecular responses: MMR.
- For all patients: time to response, duration of response, progression free survival, and overall survival.
- For all patients: safety and tolerability.
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||October 2020|
|Estimated Primary Completion Date:||October 2020 (Final data collection date for primary outcome measure)|
Drug: Ponatinib (AP24534)
45 mg tablet taken orally once daily
Other Name: AP24534
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.
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