NCT03589326

A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia

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)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 245 (actual)
• Sponsor: Takeda · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, adults with newly-diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) will receive first-line therapy of ponatinib or imatinib. The main aim of this study is to compare the number of participants on each treatment that show no signs of disease. Participants will take tablets of either ponatinib or imatinib at the same time each day combined with reduced-intensity chemotherapy for up to 20 months. Then, they will continue with single-agent therapy (ponatinib or imatinib) until they meet the discontinuation criteria from the study.

Detailed description

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 participants. Participants 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 in Argentina, Australia, Austria, Belarus, Brazil, Bulgaria, Canada, Chile, France, Mexico, Greece, Italy, Japan, Korea, Republic Of, Poland, Romania, Russia, Spain, Taiwan, Province Of China, Turkey, Finland and the United States. 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.

Conditions

• Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Interventions

Type	Name	Description
DRUG	Ponatinib	Ponatinib Tablets.
DRUG	Imatinib	Imatinib Tablets.
DRUG	Vincristine	Vincristine IV injection.
DRUG	Dexamethasone	Dexamethasone Tablets.
DRUG	Cytarabine	Cytarabine IV infusion.
DRUG	Methotrexate	Methotrexate IV infusion.
DRUG	Prednisone	Prednisone Tablets.

Timeline

• Start date: 2018-10-04
• Primary completion: 2022-08-12
• Completion: 2027-07-31
• First posted: 2018-07-17
• Last updated: 2025-11-26
• Results posted: 2023-10-27

Locations

92 sites across 20 countries: United States, Argentina, Australia, Austria, Brazil, Bulgaria, Canada, China, Finland, France, Greece, Italy, Japan, Mexico, Poland, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye)

Regulatory

• FDA-regulated drug study