Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses

Official Title

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses

Summary:

The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 milligram [mg], 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by less than or equal to (<=) 1 percent (%) Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months.

Trial Description

Primary Outcome:

  • Percentage of Participants with <=1% BCR-ABL1IS at Month 12
Secondary Outcome:
  • Percentage of Participants With Major Molecular Response (MMR) at Months 12 and 24
  • Major Cytogenetic Response (MCyR) Rates by Month 12
  • Duration of MMR
  • Percentage of Participants with Adjusted Incidence Rates for Arterial Occlusive Events (AOEs) and Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
  • Percentage of Participants With CCyR at Month 12
  • Percentage of Participants With Major Molecular Response (MMR), Molecular Response 4 (MR4) and Molecular Response (MR4.5)
  • Percentage of Participants With Molecular Response 1 (MR1) at Month 3
  • Percentage of Participants With Complete hematologic Response (CHR) at Month 3
  • Percentage of Participants with AEs Leading to Discontinuation and Dose Reduction
  • Percentage of Participants with Dose Interruptions
  • Duration of Response (DOR) of <=1% BCR-ABL1 IS
  • DOR for MMR
  • DOR in Responders
  • Time to Response
  • Percentage of Participants With Progression to AP or BP CML
  • Progression-free Survival (PFS)
  • Overall Survival (OS)
The drug being tested in this study is ponatinib. This study will characterize the safety and efficacy of ponatinib over a range of 3 starting doses. The study will enroll 276 participants in 3 cohorts and each cohort will have 92 participants. All the participants will be randomized to receive once-daily oral administration of 1 of 3 starting doses of ponatinib:
  • Cohort A: 45 mg ponatinib tablet
  • Cohort B: 30 mg ponatinib tablet
  • Cohort C: 15 mg ponatinib tablet The study is designed to consist of 2 periods: 24-cycle Main treatment period and optional treatment continuation period. Participants will be treated with their randomized dose of study drug in the Main Treatment Period until the occurrence of at least one of the following: absence of CHR by 3 months, absence of MCyR at 12 months, absence of <=1% BCR-ABL1IS at 12 months, loss of <=1% BCR-ABL1IS development of intolerance, or completion of all 24 cycles of treatment (whichever occurs first). Following completion of the 24-month main treatment period or following early withdrawal, participants may enter into an optional treatment continuation period. This multi-centre trial will be conducted in the United States, United Kingdom, Republic of Korea, Spain, France, Taiwan, Australia, Canada, Italy, Chile, Japan, Germany, Argentina, Poland, Czech Republic, Denmark, Hong Kong, Portugal, Russia, Singapore, Switzerland, and Sweden. The overall time to participate in this study is approximately 60 months. Participants will make a final visit to the clinic approximately 30 days after the last dose of study treatment.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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