Asciminib Treatment Optimization in ≥ 3rd Line CML-CP.

Official Title

A Phase 3b, Multi-centre, Open-label, Treatment Optimization Study of Oral Asciminib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Previously Treated With 2 or More Tyrosine Kinase Inhibitors.

Summary:

The purpose of the study is to optimize the treatment of asciminib in patients with chronic myelogenous leukemia in chronic phase (CML-CP) previously treated with 2 or more Tyrosine Kinase Inhibitors (TKIs). Patients for this study will be identified based on warning criteria and resistance definition following European Leukemia Network (ELN) 2020 recommendations. In addition, the study will investigate the use of two different posologies. For this, patients will receive asciminib 40 mg (twice-daily) BID or of 80 mg (once daily) once daily (QD).

Trial Description

Primary Outcome:

  • Major molecular response (MMR) rate at Week 48 for all patients with no evidence of MMR at baseline.
Secondary Outcome:
  • MMR rate at baseline at Week 12, 24, 36, 72, 96 and 144 for patients with no MMR at baseline.
  • MMR rate at Week 48 for patients with MMR at baseline
  • Time to MMR.
  • Rate of BCR-ABL1 ≤ 10%
  • Rate of BCR-ABL1 ≤1%
  • MR4 rate.
  • MR4.5 rate.
  • Rate of complete cytogenetic response (CCyR).
  • Occurrence of high-risk additional chromosomal abnormalities (ACA)
  • Cumulative molecular response rate of BCR-ABL1 ≤ 10%.
  • Cumulative molecular response rate of BCR-ABL1 ≤1%.
  • Cumulative molecular response rate of MMR.
  • Cumulative molecular response rate of MR4.
  • Cumulative molecular response rate of MR4.5.
  • Duration of MMR.
  • Duration of MR4 without loss of MMR.
  • Progression-Free survival (PFS)
  • Overall Survival (OS)
  • Treatment failure (TTF)
  • Change in symptom burden and interference from baseline over time according to the MDASI-CML PRO instrument.
This study is an international, multi-centre, non-comparative, phase IIIb, treatment optimization study of daily 80 mg asciminib (as either as 40 mg BID of asciminib or as 80 mg QD) in adult patients previously treated with 2 or more TKIs. Up to 30 patients who are intolerant to ongoing TKI treatment but in major molecular response (MMR) will also be allowed to enter the trial. Enrollment will be used to have a balance in the allocation of treatment into either asciminib 40 mg b.i.d. or 80 mg q.d. Although this trial will not be powered to compare both treatments, descriptive data from both treatment groups is expected to provide additional insight into the optimal patient management In patients not achieving MMR at 48 weeks or losing the response after the week 48 up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation. In addition, there must not be any grade 3 or 4 toxicity while on therapy, or persistent grade 2 toxicity, possibly related to asciminib and unresponsive to optimal management. The planned duration of treatment is up to 144 weeks unless patient discontinue from treatment due to unacceptable toxicity, disease progression and/or if treatment is discontinued at the discretion of the investigator or the participant prior to week 144.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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