Asciminib Used in Consolidation With Imatinib vs. Imatinib to Achieve TFR in CP-CML

NCT05413915 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: QC-TFR1-ABL001
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 4

Brief Summary

The aim of this study is to establish if consolidation of imatinib-treated patients in stable DMR through the addition of asciminib, can lead to superior rates of TFR1, compared to imatinib alone in Chronic Phase-Chronic Myelogenous Leukemia patients.

Conditions

Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, BCR/ABL-Positive; Chronic Myeloid Leukemia in Remission

Keywords

DMR

Outcome Measures

Primary Outcomes (1)

• Event-free survival rate

  Occurrence of death or loss of deep molecular response (DMR, MR4 (4-log reduction in BCR-ABL1 or better)) or loss of major molecular response (MMR, MR3 (3-log reduction in BCR-ABL1)) at any time.

  randomization until 12 months after discontinuation of all TKI among randomized patients

Secondary Outcomes (6)

• Event-free survival rate

  randomization to 6 months after discontinuation of TKI among all randomized patients

• Time to molecular relapse

  Tyrosine kinase inhibitor (TKI) discontinuation until loss of MR3 (up to 1 year)

• Molecular relapse free rate

  TKI discontinuation until loss of MR3 (up to 1 year)

• Cumulative incidence of adverse events grade ≥ 3 in each arm, using CTCAE 5.0

  from first dose/randomization until 30 days post last dose

• Association between duration of prior imatinib exposure and TFR (Treatment Free Remission) as assessed by Hazard Ratio

  from randomization until up to 12 months post consolidation

Study Arms (2)

Imatinib

ACTIVE COMPARATOR

Standard of care imatinib at 300 or 400 mg PO daily for 52 weeks

Drug: Imatinib

Imatinib and Asciminib

EXPERIMENTAL

Asciminib (60 mg PO daily for 52 weeks) will be added to standard of care imatinib (300 or 400 mg PO daily for 52 weeks)

Drug: Asciminib; Drug: Imatinib

Interventions

Asciminib DRUG

Tyrosine kinase inhibitor

Also known as: ABL-001

Imatinib and Asciminib

Imatinib DRUG

Tyrosine kinase inhibitor

Also known as: Imatinib mesylate

Imatinib; Imatinib and Asciminib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible, candidates must fulfill all the following criteria:
• Male or female patients aged at least 18 years of age with a confirmed diagnosis of CML-CP.
• Written informed consent prior to any screening procedures
• Available and willing to comply with all study assessments.
• Imatinib treatment ongoing \> 4 years, and currently receiving:
• Standard dose 400 mg PO QD or;
• mg PO QD for at least 6 months (see below)
• CML in deep molecular response (DMR, at least MR4 IS) for at least 12 months prior to randomization (documented through at least 3 PCRs test results over the period of 12 months prior to randomization, showing BCR-ABL1 levels ≤ 0.01% IS (International Scale) and no result over \>0.01%). For patients receiving 300 mg imatinib QD, minimum of two (2) of those qPCRs evaluations must have been obtained at least 3 months apart while on 300 mg imatinib.
• ECOG performance status of 0-2.
• Adequate organ function, defined by:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L (without the requirement for transfusion for 14 days)
• Hemoglobin ≥ 90 g/L (without the requirement for transfusion for 14 days)
• Serum creatinine \< 132 µmol/L
• Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN)

You may not qualify if:

• Patients known to be in second CP-CML after previous progression to AP/BC-CML
• Previous treatment with a TKI other than imatinib.
• Prior allogeneic transplant.
• Tolerance concerns to continue imatinib on study, as determined by the investigator.
• Treatment with strong inducers/inhibitors of CYP3A4.
• Known atypical ABL1-BCR transcript that precludes use of IS system for monitoring.
• Current or prior history of another malignancy within the past 2 years, unless it is a solid tumor with a life expectancy of at least 3 years and its treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (for example, patients who have undergone complete resection of an in situ carcinoma, or who have a low risk indolent prostate cancer are eligible). History or current diagnosis of cardiac disease indicating significant risk or safety for subjects participating in the study such as:
• History of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
• Concomitant clinically significant arrhythmias
• Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to randomization
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• i. Risk factors for Torsades de Pointes ii. Concomitant medications with a "known" risk of Torsades de Pointes iii. inability to accurately determine the QTcF interval, unless this is due to the presence of a pacemaker.
• History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis; on-going acute liver disease or history of chronic liver disease
• Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Subjects with other severe or uncontrolled medical conditions that in the opinion of the investigator may compromise their compliance with the protocol or may represent an unacceptable risk to their safety (e.g. uncontrolled diabetes, active or uncontrolled infection, uncontrolled clinically significant hyperlipidemia and high serum amylase).

Sponsors & Collaborators

• Sarit Assouline: lead
• Novartis: collaborator

Study Sites (4)

Hôpital Maisonneuve-Rosemont (CIUSSS EMTL)

Montreal, Quebec, H1T 2M4, Canada

Location

Clinical Research Unit - Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Hôpital Enfant-Jésus - CHUQ

Québec, Quebec, G1J 1Z4, Canada

Location

Hôpital Fleurimont - CHUS (CIUSSS Estrie)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Sarit E Assouline, MD, MSc

  SMBD Jewish General Hospital CIUSSS West Central Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: 2 study phases: * Consolidation phase: 52 weeks of consolidation treatment on study with asciminib 60 mg PO QD in addition to current dose mg imatinib (300 or 400 mg PO QD) vs. current dose imatinib alone. * TFR follow up phase: all participants attempting TFR to be followed for CML remission status.

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 10, 2022
• Study Start: November 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

CA (4)