Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation

NCT06427811 | Completed Phase 4

• 1 other identifier: CABL001A2005
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 10

Brief Summary

The Drugs Controller General of India (DCGI) has granted approval for Asciminib film-coated 40 mg tablets on 20 Oct 2023 with the condition to perform a Phase IV clinical study in Indian patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) per the India Prescribing Information (PI). The purpose of this prospective, multicenter, single-arm, open-label, Phase IV study is, therefore, to confirm the safety and efficacy of Asciminib in Indian patients with Ph+ CML-CP (without threonine-315 residue with isoleucine \[T315I\] mutation), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) and patients with Ph+ CML-CP with T315I mutation.

Conditions

Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase

Keywords

ABL001; Asciminib; Ph+ CML-CP; T315I mutation; Ph+ CML-CP without T315I mutation; Ph+ CML-CP with the T315I mutation; Myelogenous; Chronic; Chronic Myeloid Leukemia; Ph1 Positive Myeloid Leukemia; Philadelphia Positive Myeloid Leukemia; BCR-ABL Positive; Post-authorization Interventional Study; Tyrosine Kinase Inhibitors; TKI; Chronic Leukemia; Ph1 Positive Leukemia; Without T315I mutation; with the T315I mutation

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of adverse events(AEs)/serious AEs (SAEs) in participants with Ph+ CML-CP without T315I mutation

  Frequency and severity of adverse events(AEs)/serious AEs (SAEs) in participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs up to 6 months

  up to 6 months

• Frequency and severity of AEs/SAEs in participants with Ph+ CML-CP with T315I mutation

  Frequency and severity of AEs/SAEs in participants with Ph+ CML-CP with T315I mutation up to 6 months

  up to 6 months

Secondary Outcomes (32)

• Percentage of participants with dose interruptions, reductions, and discontinuation (without T3151 mutation)

  up to 6 months

• Percentage of participants achieving a complete hematologic response (CHR) at 3 and 6 months (without T3151 mutation)

  3 months, 6 months

• Percentage of participants achieving early molecular response (EMR) at 3 and 6 months (without T3151 mutation)

  3 months, 6 months

• Percentage of participants achieving molecular response (MR2) at 3 and 6 months (without T3151 mutation)

  3 months, 6 months

• Percentage of participants achieving major molecular response (MMR) at 3 and 6 months (without T3151 mutation)

  3 months, 6 months

Study Arms (1)

Asciminib

EXPERIMENTAL

Participants without T315I mutation will receive 80 mg once daily at approximately the same time each day OR 40 mg twice daily per Investigator's discretion at approximately 12-hour intervals. Participants with T315I mutation will receive200 mg twice daily at approximately 12-hour intervals.

Drug: Asciminib

Interventions

Asciminib DRUG

Film-coated tablets with 40 mg dose strength taken orally

Also known as: ABL001

Asciminib

Eligibility Criteria

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

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Male or female participants ≥18 years of age at the screening visit with a confirmed diagnosis of Ph+ CML-CP.
• Participants must meet all of the following laboratory values as confirmed by the available reports of the peripheral blood test or bone marrow examination (performed within 12 months before the screening) at the screening visit to meet the criteria of Ph+ CML-CP:
• \<15% blasts in peripheral blood and/or bone marrow
• \<30% blasts plus promyelocytes in peripheral blood and/or bone marrow
• \<20% basophils in the peripheral blood
• ≥50 x 109/L (≥50,000/mm3) platelets#
• No evidence of extramedullary leukemic involvement, apart from hepatosplenomegaly.
• #Transient prior therapy related thrombocytopenia (\<50,000/mm3 for ≤30 days prior to screening) is acceptable.
• \- a. For Ph+ CML-CP participants with T315I mutation, mutational analysis testing at any time point showing a documented T315I mutation.
• b. For Ph+ CML-CP participants without T315I mutation, at least 2 prior ATP-site TKIs (i.e., imatinib, nilotinib, bosutinib, dasatinib, or ponatinib) with failure\* (adapted from the 2020 European LeukemiaNet \[ELN\] Recommendations) or intolerance\*\* to the most recent TKI therapy at the time of screening.
• \*Failure for Ph+ CML-CP participants (CP at the time of initiation of last therapy) is defined as meeting at least one of the following criteria:
• Three months after the initiation of therapy: \>10% BCR::ABL1 on IS if confirmed within 1-3 months
• Six months after the initiation of therapy: BCR::ABL1 ratio \>10% IS
• Twelve months after initiation of therapy: BCR::ABL1 ratio \>1% IS

You may not qualify if:

• Known second chronic phase of CML after previous progression to CML-AP/CML-BC.
• Previous treatment with a hematopoietic stem-cell transplantation.
• Cardiac or cardiac repolarization abnormality, including any of the following:
• History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
• QT corrected for heart rate by Fridericia's cube root formula (QTcF) at screening ≥450 msec (both male and female participants)
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• Inability to determine the QTcF interval.1. Known second chronic phase of CML after previous progression to CML-AP/CML-BC.
• Previous treatment with a hematopoietic stem-cell transplantation.
• Cardiac or cardiac repolarization abnormality, including any of the following:
• History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
• QT corrected for heart rate by Fridericia's cube root formula (QTcF) at screening ≥450 msec (both male and female participants)
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Ahmedabad, Gujarat, 380009, India

Location

Novartis Investigative Site

Ahmedabad, Gujarat, 382428, India

Location

Novartis Investigative Site

Bengaluru, Karnataka, 560034, India

Location

Novartis Investigative Site

Trivandrum, Kerala, 695 011, India

Location

Novartis Investigative Site

Pune, Maharashtra, 422001, India

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 431005, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500082, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700014, India

Location

Novartis Investigative Site

Cuttack, 753007, India

Location

Novartis Investigative Site

Guwahati, 781003, India

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; 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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: November 28, 2024
• Primary Completion: March 18, 2026
• Study Completion: March 18, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IN (10)