Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

NCT04666259 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CABL001AUS04
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 26

Brief Summary

This study was a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI

Conditions

Chronic Myelogenous Leukemia - Chronic Phase

Keywords

CML; T315I mutation; CP; Asciminib,; BCR-ABL,; ABL001,; CML-AP,; ELN; MMR; Molecular Response; MR4.5; MR4; RQ-PCR; AIM4CML,; tyrosine Kinase Inhibitor; TKI; adult

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A and B up to 24 Weeks

  Adverse events (AEs) and serious adverse events (SAEs) are summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) are reported as adverse events and or serious adverse events as determined by the investigator.

  Baseline to up to 24 Weeks

Secondary Outcomes (11)

• Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A, B and C by Week 48

  Baseline up to 48 weeks

• Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A, B and C by Week 72

  Baseline up to 72 weeks

• Percentage of Patients Achieving Complete Hematologic Response (CHR) for Cohorts A, B and C

  Baseline to 12, 24, 48, 72 weeks

• Percentage of Patients Achieving Major Molecular Response (MMR) for Cohorts A, B and C

  Baseline up to 12, 24, 48, 72 weeks

• Percentage of Patients Achieving Molecular Response (MR2) for Cohorts A, B and C

  Baseline up to 12, 24, 48, 72 weeks

Study Arms (3)

Cohort A

EXPERIMENTAL

40 mg asciminib orally twice daily (BID)

Drug: ABL001

Cohort B

EXPERIMENTAL

80 mg asciminib orally once daily (QD)

Drug: ABL001

Cohort C

EXPERIMENTAL

200 mg asciminib orally twice daily (BID)

Drug: ABL001

Interventions

ABL001 DRUG

Asciminib will be supplied as 20 mg or 40 mg strength tablets will be administered orally in accordance with the assigned cohort.

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained and signed prior to participation in the study
• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Patients must meet all of the following laboratory values at the screening visit:
• \< 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
• Transient prior therapy related thrombocytopenia (\< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Mutation Analysis testing performed 6 months before study entry
• Prior treatment with a minimum of:
• prior ATP-site TKIs (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of absence of T315I mutation
• prior ATP site TKI (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of presence of T315I mutation
• Failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
• Failure for CML-CP patients (CP at the time of initiation of last therapy) is defined as meeting at least one of the following criteria.

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Known second chronic phase of CML after previous progression to AP/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, coronary artery bypass graft (CABG)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
• QTcF at screening ≥450 msec (male patients), ≥460 msec (female patients)
• 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
• Concomitant medication(s) with a "Known risk of Torsades de Pointes" per wwwcrediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
• Inability to determine the QTcF interval
• Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, pulmonary hypertension)
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
• History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (26)

Alaska Oncology and Hematology

Anchorage, Alaska, 99508, United States

Location

Arizona Oncology Associates

Phoenix, Arizona, 85016, United States

Location

Cancer Treatment Centers of America

Phoenix, Arizona, 85027, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Lundquist Inst BioMed at Harbor

Torrance, California, 90509-2910, United States

Location

Rocky Mountain Cancer Centers

Boulder, Colorado, 80304, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists East

Stuart, Florida, 34994, United States

Location

Florida Cancer Specialists Pan

Tallahassee, Florida, 32308, United States

Location

Indiana Blood and Marrow Institute

Beech Grove, Indiana, 46107, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Uni of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Michigan Med University of Michigan

Ann Arbor, Michigan, 48109 5271, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Uni of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Northwest Cancer Specialists

Portland, Oregon, 97210, United States

Location

Texas Oncology

Dallas, Texas, 75251, United States

Location

Texas Oncology P A

Fort Worth, Texas, 76104, United States

Location

Univ of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

asciminib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; 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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Cohort A and B will be randomized but not C
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: May 25, 2021
• Primary Completion: June 20, 2023
• Study Completion: June 26, 2024
• Last Updated: October 16, 2025
• Results First Posted: July 12, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (26)