Official Title
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
Summary:
The study is designed to compare the efficacy of asciminib 80 mg QD versus 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 following treatment options 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.
Trial Description
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.
View this trial on ClinicalTrials.gov
