NCT04971226

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

A Phase III, Multi-center, 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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 405 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected Tyrosine Kinase Inhibitor (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. This study has three periods: 1. Treatment period for all randomized participants, 2. Optional Treatment-Free Remission (TFR) period only for participants meeting TFR eligibility criteria and 3. Treatment Re-Initiation (TRI) period only for participants who relapsed after TFR attempt.

Detailed description

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. Approximately 402 patients will be randomized in a 1:1 ratio to asciminib and Investigator selected TKI to join the treatment period. 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. The stratified randomization based on these two stratification factors will help to achieve a balance across the treatment arms for the possible comorbidities and baseline characteristics of patients enrolled in the study. 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. Apart from the treatment period described above, the present study comprises an optional Treatment-Free Remission (TFR) Period enrolling consenting participants of the treatment period (receiving asciminib or IS-TKI) who will discontinue their randomized treatment if they meet per protocol eligibility criteria. The optional TFR Period will last at least 2 years to assess the feasibility of TFR and TFR outcomes following discontinuation of their randomized treatment (asciminib or IS-TKI). In addition, during the TFR Period, participants who will lose major molecular response (MMR) must re-initiate treatment and will enter into a Treatment Reinitiation (TRI) Period. During the treatment period, no crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed. For specifically participants who must transition into the TRI Period, at the time of treatment re-initiation: a) participants who were previously treated with asciminib will resume asciminib at the same dose prior to entry into TFR. b) participants who were on IS-TKI may either continue with the same study treatment they were randomized to and at the same dose prior to entry into TFR or may switch to asciminib with a starting dose of 80 mg QD. Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, premature discontinuation due to treatment failure, disease progression or intolerance, due to Investigator or participant decision. or due to patient going to TFR Period and/or TRI Period. Duration of study: The End of Study will occur 8 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.

Conditions

• Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive

Interventions

Type	Name	Description
DRUG	Imatinib	Comes in 100 mg and 400 mg tablets and taken orally
DRUG	Nilotinib	Comes in 150 mg and 200 mg capsules and taken orally
DRUG	Bosutinib	Comes in 100 mg and 400 mg tablets and taken orally
DRUG	Dasatinib	Comes in 20 mg, 50 mg, 70 mg and 100 mg tablets and taken orally
DRUG	Asciminib	Comes in 40 mg tablets and taken orally

Timeline

• Start date: 2021-10-06
• Primary completion: 2023-11-28
• Completion: 2031-01-18
• First posted: 2021-07-21
• Last updated: 2026-04-06
• Results posted: 2025-03-10

Locations

110 sites across 29 countries: United States, Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Norway, Portugal, Singapore, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study