An Efficacy Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Participants With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
The purpose of this study is to compare the efficacy of ponatinib versus imatinib, administered as first-line therapy in combination with reduced-intensity chemotherapy, in participants with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), as measured by the minimal residual disease (MRD)-negative complete remission (CR) at the end of induction.
The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat people who have newly diagnosed Ph+ ALL. This study will look at the efficacy of ponatinib in participants in addition to standard care.
The study will enroll approximately 230-320 patients. Patients will be randomized in a 2:1 ratio to receive oral ponatinib or imatinib (Cohort A and Cohort B, respectively) daily throughout the study.
All participants will be asked to take ponatinib or imatinib at the same time each day with reduced-intensity chemotherapy in induction phase (Cycles 1 to 3), consolidation phase (Cycles 4 to 9) and maintenance phase (Cycles 10 to 20). At the end of the 20 cycles, participants will remain on ponatinib or imatinib (administered as a single agent). The dose of ponatinib in consolidation and maintenance phase will start with the last dose given in the previous phase. The dose can be modified based on MRD-negative CR results.
This multi-center trial will be conducted worldwide. Participants including those who achieve a clinical response, may receive study drug until they are deceased, have failed to achieve the primary endpoint, have experienced relapse from CR or have progressive disease, have an unacceptable toxicity, have withdrawn consent, have proceeded to HSCT, or until the sponsor terminates the study, whichever occurs first. After disease progression, all participants will be contacted every 3 months for survival follow-up. Participants will be followed until completion of the study or until the participant's death has been reported.
Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 320 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: It is an open-label trial, therefore investigators and participants are unblinded.
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Actual Study Start Date: August 10, 2018
Estimated Primary Completion Date: July 15, 2020
Estimated Study Completion Date: January 15, 2026
- Experimental: Cohort A: Ponatinib 30 milligram (mg)
- Active Comparator: Cohort B: Imatinib
|Date last updated at source||2019-03-04|
|Study start date||2018-08-10|
|Estimated primary completion date||2020-07-15|