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.
Name: Ponatinib
Description: 45 mg dose taken orally once dailyType: DrugCP-CML R/I AP-CML R/I Blast Phase (BP) CML / Ph+ ALL CP-CML with T315I mutation AP-CML with T315I mutation BP-CML / Ph+ ALL with T315I mutation
Description: Defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR).
Measure: Major cytogenetic response (MCyR) in CP-CML patients Time: up to 48 months after first doseDescription: Consists of complete hematologic response (CHR) or no evidence of leukemia (NEL)
Measure: Major hematologic response (MaHR) in AP-CML patients Time: up to 48 months after first doseDescription: Consists of CHR or NEL
Measure: MaHR in BP-CML/Ph+ALL patients Time: up to 48 months after first doseDescription: The composite of: Hematologic responses: CHR; Cytogenetic responses: confirmed MCyR; and Molecular response: major molecular response (MMR).
Measure: Responses in CP-CML patients Time: up to 48 months after first doseDescription: The composite of: Cytogenetic responses: CCyR, PCyR, confirmed MCyR; and Molecular response: MMR.
Measure: Responses in AP-CML or BP-CML/Ph+ ALL patients Time: up to 48 months after first doseDescription: The composite of time to response, duration of response, progression free survival, and overall survival.
Measure: Responses in all patients Time: up to 48 months after first doseDescription: The Adverse Event (AE) incidence rates as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described for each cohort of the trial. Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented.
Measure: Safety and tolerability for all patients Time: up to 48 months after first doseAllocation: Non-Randomized
Single Group Assignment
There is one SNP
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL) 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. --- T315I ---
- 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) - 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 - Underwent major surgery within 14 days prior to first dose of ponatinib - Have ongoing or active infection - Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug Chronic Myeloid Leukemia Ph+ Acute Lymphoblastic Leukemia Leukemia Leukemia, Myeloid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive 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 the BCR-ABL gene (BCR-ABL). --- T315I ---
This Phase 1 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. --- T315I ---