A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

Titre officiel

A Phase III, Multi-centre, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase

Sommaire:

L’étude a pour but de comparer l’efficacité de l’asciminib 80 mg QD par rapport aux TKI sélectionnés par les chercheurs pour le traitement des patients nouvellement diagnostiqués, précédemment non traités, atteints de LMC Ph+ en phase chronique. Le TKI sélectionné par le chercheur sera l’une des options thérapeutiques suivantes pour le traitement de première intention de la LMC en phase chronique : imatinib 400 mg QD ou nilotinib 300 mg BID ou dasatinib 100 mg QD ou bosutinib 400 mg QD.

Description de l'essai

Primary Outcome:

  • Major Molecular Response (MMR) at week 48
Secondary Outcome:
  • Major Molecular response at week 96
  • Time to discontinuation of study treatment due to Adverse Events (TTDAE)
  • Major Molecular response at scheduled data collection time points
  • Major Molecular response by scheduled data collection time points
  • MR4.0 at scheduled data collection time points
  • MR4.5 at all scheduled data collection time points
  • MR4.0 by scheduled data collection time points
  • MR4.5 by all scheduled data collection time points
  • Complete Hematological response (CHR) at all scheduled data collection time points
  • Complete Hematological response (CHR) by all scheduled data collection time points
  • Complete Cytogenic response (CCyR) at Week 48 & Week 96
  • Complete Cytogenic response (CCyR) by Week 48 & Week 96
  • Duration of MMR
  • Duration of MR4.0
  • Duration of MR4.5
  • Time to first MMR
  • Time to first MR4.0
  • Time to first MR4.5
  • Time to treatment failure (TTF)
  • Failure Free Survival (FFS)
  • Event Free Survival (EFS)
  • Progression Free Survival (PFS)
  • Overall Survival (OS)
  • Trough plasma concentrations.
  • Pharmacokinetics (PK) of Asciminib: Cmax
  • PK of Asciminib: Tmax
  • PK of Asciminib: AUCtau and AUClast
  • PK of Asciminib: CL/F
  • Change from baseline in overall scores and individual scales of the EORTC QLQ-C30
  • Change from baseline in overall scores and individual scales of the EORTC QLQ-CML24

This study is a phase III, multi-center, open-label, randomized study of oral asciminib 80 mg QD versus Investigator selected TKI (imatinib, nilotinib, dasatinib, or bosutinib) in adult patients with newly diagnosed Ph+ CML-CP. All comparator TKIs will be made available, unless not permitted by local regulations or local Health Authority, or not approved for the treatment of CML in the country.

The study is designed to compare the efficacy of asciminib 80 mg QD with Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the treatment options approved by major Health Authorities for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.

Approximately 402 patients will be randomized in a 1:1 ratio to asciminib and Investigator selected TKI.

Randomization will be stratified based on the following two stratification factors:

  • ELTS score (low versus intermediate versus high)
  • Pre-randomization selected TKI (imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib)).

Prior to randomization, the Investigator, in consultation with the patient, considering the current treatment paradigm and patient characteristics and comorbidities, will make a selection of preference for imatinib or 2G TKI (nilotinib or dasatinib or bosutinib) if the patient is randomized to the comparator arm.

To further ensure that the distribution of patients, between imatinib and 2G TKIs (nilotinib or dasatinib or bosutinib), in the Investigator selected TKI arm is reflective of the use of these agents in clinical practice, the enrollment into the strata of imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib) based on the pre-randomization selection of TKI will be managed by Interactive Response Technology to be approximately 50% versus 50%.

Treatment arms: The study will have 2 treatment arms:

  • Arm 1: asciminib 80 mg QD under fasting conditions
  • Arm 2: Investigator selected TKI that will include one of the below treatments:
  • Imatinib 400 mg QD administered with food
  • Nilotinib 300 mg BID administered under fasting conditions
  • Dasatinib 100 mg QD administered with or without meal
  • Bosutinib 400 mg QD administered with food.

No crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed.

Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, or until premature discontinuation due to treatment failure, disease progression or intolerance or due to Investigator or participant decision.

Duration of study: The End of Study will occur 5 years from the last patient first treatment in the study. Patients who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to AP/BC) until the End of Study.

Voir cet essai sur ClinicalTrials.gov

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