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 and safety of ponatinib in participants with resistant chronic myeloid leukemia (CML) in chronic phase (CP) in a range of doses.

Trial Description

Primary Outcome:

  • Percentage of Participants with Less than or Equal to (<=) 1 Percent (%) Breakpoint Cluster Region-Abelson Transcript Level as Measured by International Scale (BCR-ABL 1IS) at Month 12
Secondary Outcome:
  • Major Molecular Response (MMR) Rates at Months 12 and 24
  • Major Cytogenetic Response (MCyR) Rates at Month 12
  • Duration of MMR
  • Percentage of Participants with Arterial Occlusive Events (AOEs) and Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
  • Safety Measured by Comparing Frequencies of AEs, SAEs and VOEs, AOEs and VTEs
  • Analysis of the Relationship Between Steady-state Plasma Ponatinib Exposure [Peak Plasma Concentration (Cmax) and Area-under-the-curve (AUC)] and Safety measures (AOEs and VTEs and any AEs that occur in at least 30 participants)
  • Analysis of the Relationship between Steady-state Plasma Ponatinib Exposure (AUC and Cmax) and Efficacy Measures (including ≤1% BCR-ABL 1IS, MCyR, and MRR
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 complete hematologic response (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 worldwide. 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

These resources are provided in partnership with the Canadian Cancer Society