Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia

NCT05384587 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: CABL001AUS08
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 80

Brief Summary

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP- binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.

Conditions

Chronic Myelogenous Leukemia - Chronic Phase

Keywords

CML; Chronic Phase; Asciminib; ASC2ESCALATE; T315I mutation; BCR-ABL; MMR; TKI; Tyrosine Kinase Inhibitor; molecular response; adult

Outcome Measures

Primary Outcomes (1)

• Percentage of participants who achieve Major Molecular Response (MMR) in the 2L setting

  MMR is defined as BCR::ABL1IS ≤ 0.1%. A patient will be counted as having achieved MMR at 12 month if he/she meets the MMR criterion at 12 month.

  Baseline up to 12 months

Secondary Outcomes (15)

• Percentage of participants achieving Molecular Response 4.5 (MR4.5) at 24 and 36 months

  Baseline, 24 and 36 months

• MMR Rate at visit (other than 12 month)

  Baseline, 3, 6, 18, 24, 30 and 36 months

• MR2 Rate at visit

  Baseline, 3, 6, 12, 18, 24, 30 and 36 months

• MR4 Rate at visit

  Baseline, 3, 6, 12, 18, 24, 30 and 36 months

• MR4.5 Rate at visit

  Baseline, 3, 6, 12, 18 and 30 months

Study Arms (1)

Asciminib

EXPERIMENTAL

80 mg initial oral dose taken once a day with possible dose escalation

Drug: asciminib

Interventions

asciminib DRUG

Supplied in 40 mg and 100 mg tablets for oral use to be taken daily. Dose may be increased at 6 and 12 months based on molecular response with BCR-ABL1 Polymerase Chain Reaction testing.

Also known as: ABL001

Asciminib

Eligibility Criteria

• Age: 18 Years - 100 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
• CML-CP, no previous AP or BC
• ≥ 18 years of age
• ECOG performance status of 0, 1 or 2
• Adequate end organ function within 14 days before the first dose of asciminib treatment.
• Patients with mild to moderate renal and hepatic impairment are eligible if:
• Total bilirubin ≤ 3.0 x ULN without AST/ALT increase
• Aspartate transaminase (AST) ≤ 5.0 x ULN
• Alanine transaminase (ALT) ≤ 5.0 x ULN
• Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
• Alkaline phosphatase ≤ 2.5 x ULN
• Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft- Gault formula
• Criteria #6 and 7 are specific to the 2L patient cohort. These are meant to be either/or. It is not required to have both criteria satisfied.
• Warning or failure (according to 2020 ELN Recommendations; Hochhaus et al) to 1L TKI therapy at the time of screening
• a. Warning is defined as: i. Six months after the initiation of treatment: BCR::ABL1IS \>1-10% ii. Twelve months after the initiation of treatment: BCR::ABL1IS \>0.1-1% b. Treatment failure/resistance to 1L TKI is defined as: i. BCR::ABL1IS \>10% if 1L treatment duration between 6 and 12 months ii. BCR::ABL1IS \>1% if 1L treatment longer than 12 months treatment iii. Beyond 12 months after initiation of treatment: loss of MMR

You may not qualify if:

• Previous treatment
• With 2 or more ATP-binding site TKIs (for 2L patient cohort)
• More than 4 weeks with 1-ATP-binding site TKIs (for 1L patient cohort)
• Previous treatment with asciminib
• Known presence of the T315I mutation at any time prior to study entry
• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a hematopoietic stem-cell transplantation
• Patient planning to undergo allogeneic 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), ≥450 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 www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (80)

University of Alabama at Birmingham

Birmingham, Alabama, 35233-0271, United States

Location

Alaska Oncology and Hematology

Anchorage, Alaska, 99508, United States

Location

City of Hope Phoenix

Scottsdale, Arizona, 85258, United States

Location

USO Arizona Oncology

Tucson, Arizona, 85711, United States

Location

Onco Inst of Hope and Innovation

Cerritos, California, 90703, United States

Location

City of Hope National Medical

Duarte, California, 91010, United States

Location

UCSF Fresno Internal Medicine

Fresno, California, 93701, United States

Location

Virginia K Crosson Cancer Center

Fullerton, California, 92835, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Alta Bates Summit Medical Center

Oakland, California, 94609, 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

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

The Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists East

Stuart, Florida, 34994, United States

Location

City Of Hope Atlanta

Atlanta, Georgia, 30033, United States

Location

Emory University School of Medicine Winship Cancer Institute

Atlanta, Georgia, 30308, United States

Location

Augusta University Georgia

Augusta, Georgia, 30912, United States

Location

Northwest Georgia Oncology Center

Marietta, Georgia, 30060, United States

Location

Franciscan Health Indianapolis

Indianapolis, Indiana, 42637, United States

Location

Investigative Clinicl Rsrch of Indi

Indianapolis, Indiana, 46260, United States

Location

Holden Comp Can Cent Quad Cities U

Iowa City, Iowa, 52242, United States

Location

Wichita Community Clcl Onco Program

Wichita, Kansas, 67214, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Louisiana State University

Shreveport, Louisiana, 71130, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202-2689, United States

Location

Jackson Onc Associates

Jackson, Mississippi, 39216, United States

Location

University Missouri Ellis Fischel Cancer Center

Columbia, Missouri, 65203, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

St Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Nebraska Hematology Oncology P C

Lincoln, Nebraska, 68506, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Care Access Research Clifton

Clifton, New Jersey, 07013, United States

Location

Hackensack Meridian Health

Edison, New Jersey, 88837, United States

Location

Hackensack University Medical Ctr

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of NJ

New Brunswick, New Jersey, 08901, United States

Location

UNM

Albuquerque, New Mexico, 87102, United States

Location

Clinical Research Alliance

Lake Success, New York, 11042, United States

Location

NYU Langone Long Island

Mineola, New York, 11501, United States

Location

Manhattan Hematol Oncol Associates

New York, New York, 10016, United States

Location

Mt Sinai Medical Center

New York, New York, 10029-6574, United States

Location

New York Bld And Cancer Specialists

Port Jefferson, New York, 11776, United States

Location

SUNY Stony Brook Medical Oncology

Stony Brook, New York, 11794-8174, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Novant Health Heart Vas Inst

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Uni Health Sci

Winston-Salem, North Carolina, 27157, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Hematology Oncology Care

Cincinnati, Ohio, 45236, United States

Location

James Cancer Hospital and Solove Research Institute Ohio State

Columbus, Ohio, 43210, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Care Access Research

Easton, Pennsylvania, 18045, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Bon Secours Cancer Center

Greenville, South Carolina, 29607, United States

Location

Avera Cancer

Sioux Falls, South Dakota, 57105, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology P A

Austin, Texas, 78121, United States

Location

Texas Oncology

Dallas, Texas, 75251, United States

Location

Ctr For Cancer And Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Univ of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Texas Oncology San Antonio

San Antonio, Texas, 78258, United States

Location

Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States

Location

Community Cancer Trials of Utah

Ogden, Utah, 84405, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists

Gainesville, Virginia, 20155, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Fred Hutch Cancer Research

Seattle, Washington, 98109, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Dean Health System

Madison, Wisconsin, 53717, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Atallah EL, Mauro MJ, Sasaki K, Levy MY, Koller P, Yang D, Laine D, Sabo J, Gu E, Cortes JE. Dose-escalation of second-line and first-line asciminib in chronic myeloid leukemia in chronic phase: the ASC2ESCALATE Phase II trial. Future Oncol. 2024;20(38):3065-3075. doi: 10.1080/14796694.2024.2402680. Epub 2024 Oct 10.

  PMID: 39387441 DERIVED

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

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 20, 2022
• Study Start: November 11, 2022
• Primary Completion: August 13, 2025
• Study Completion (Estimated): October 17, 2027
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (80)