ASC2ESCALATE (CABL001AUS08) = Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia [USA]

What is the purpose of the study

This is a study to evaluate oral asciminib in patients with CML in chronic phase (CP) who have been previously treated with one prior ATP- binding site tyrosine kinase inhibitor (TKI) with discontinuation due to treatment failure, warning or intolerance  [second line (2L) patient cohort].

This study also gains insights into the effect of asciminib when used in first line (1L) treatment. To this end, newly diagnosed CML-CP patients who may have received a TKI for up to 4 weeks are included in a separate 1L patient cohort.

What will happen during the study

This trial consists of three periods: screening and baseline for up to 28 days, treatment with ascimib for up to 104 weeks and a safety follow up period for 30 days.

Patients with CML-CP without T315I mutation who had received 1 prior ATP-binding site TKI will be considered for inclusion in the 2L patient cohort of this trial.

In addition, newly diagnosed CML-CP patients will be considered for inclusion in a separate 1L patient cohort.

All eligible patients will initially receive asciminib 80 mg once daily. At 6 months of study treatment, patients who have achieved BCR-ABL1IS ≤1% will continue on the same dose whereas those who have not achieved this will increase their dose to 200 mg once daily.

At 12 months of study treatment, patients will be evaluated for the primary endpoint of the study (MMR at 12 month in 2L patient cohort). They will then:

• continue on the current dose of asciminib if MMR is achieved, or
• increase dose to 200 mg once daily if they are on 80 mg once daily dosing and have not achieved MMR, or
• increase dose to 200 mg twice daily if they are on 200 mg once daily dosing and have not achieved MMR, or
• be taken off the study and switched to Investigator’s agent of choice if MMR is not achieved and it is in the interest of the patient based on investigator’s clinical judgment.

Key inclusion criteria

This study includes patients of all sexes who:

• are aged 18 years or older
• have chronic myelogenous leukemia in chronic phase (CML-CP), no previous accelerated phase (AP) or blast crisis (BC)
• have an Eastern Co-Operative Group (ECOG) status of 0, 1 or 2
• have adequate end organ function within 14 days before the first dose of asciminib treatment.

Further criteria apply. Please discuss these with your doctor or study staff.

Key exclusion criteria

This study does not include patients who:

• have been treated
  – with 2 or more ATP-binding site TKIs (for second line patient cohort)
  – more than 4 weeks with 1-ATP-binding site TKIs (for first line patient cohort)
• have been treated previously with asciminib
• have known presence of a T315I mutation at any time before study entry
• have a known second chronic phase of CML after previous progression to AP/BC.

Further criteria apply. Please discuss these with your doctor or study staff.

Estimated primary completion date

Where can I find additional information

You can find a study description in the US registry ClinicalTrials.gov. This is a database provided by the U. S. National Institutes of Health.

Study centers / principal investigators

United States

Alabama

University of Alabama at Birmingham
Birmingham, Alabama, 35233-0271
Principal Investigator: Omer Jamy

Alaska

Alaska Oncology and Hematology
Anchorage, Alaska, 99508
Principal Investigator: Steven Liu

California

Onco Inst of Hope and Innovation
Cerritos, California, 90703
Principal Investigator: Arati Rani Chand

City of Hope National Medical
Duarte, California, 91010
Principal Investigator: Paul Koller

UCSF Fresno Internal Medicine
Fresno, California, 93701
Principal Investigator: Haifaa Abdulhaq

Virginia K Crosson Cancer Center
Fullerton, California, 92835
Principal Investigator: Steven Kim

UCLA
Los Angeles, California, 90095
Principal Investigator: Gary Schiller

Lundquist Inst BioMed at Harbor
Torrance, California, 90509-2910
Principal Investigator: Sarah Tomassetti

Colorado

Rocky Mountain Cancer Centers USOR
Bolder, Colorado, 80304
Principal Investigator: David J. Andorsky

Florida

Florida Cancer Specialists
Fort Myers, Florida, 33901
Principal Investigator: Blessy Jacob

Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207
Principal Investigator: Maxim Norkin

Florida Cancer Specialists North
Saint Petersburg, Florida, 33705
Principal Investigator: Gustavo Alfonso Fonseca

Florida Cancer Specialists East
Stuart, Florida, 34994
Principal Investigator: Shachar Peles

Georgia

Emory University School of Medicine/Winship Cancer Institute
Atlanta, Georgia, 30308
Principal Investigator: Anthony Michael Hunter

Augusta University Georgia
Augusta, Georgia, 30912
Principal Investigator: Jorge Cortes

Northwest Georgia Oncology Center
Marietta, Georgia, 30060
Principal Investigator: Steve McCune

Indiana

Franciscan Health Indianapolis
Indianapolis, Indiana, 42637
Principal Investigator: Brian Mulherin

Kansas

Wichita Community CIcI Onco Program Oncology
Wichita, Kansas, 67214
Principal Investigator: Shaker R Dakhil

Kentucky

University of Kentucky
Lexington, Kentucky, 40536
Principal Investigator: Reinhold Munker

Louisiana

Louisiana State University Main Centre
Shreveport, Louisiana, 71130
Principal Investigator: Poornima Ramadas

Massachusetts

Dana Farber Cancer Center
Boston, Massachusetts, 02215
Principal Investigator: Marlise Luskin

Mississippi

Jackson Onc Associates
Jackson, Mississippi, 39216
Principal Investigator: Thomas Williamson

Missouri

University Missouri Ellis Fischel Cancer Center
Columbia, Missouri, 65203
Principal Investigator: Hildebrandt Gerhard

Siteman Cancer Center
Saint Louis, Missouri, 63110
Principal Investigator: Camille N Abboud

Montana

St Vincent Frontier Cancer Center
Billings, Montana, 59102
Principal Investigator: Patrick Cobb

New Hampshire

Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Principal Investigator: Swaroopa Yerrabothala

New Jersey

Hackensack Meridian Health Research
Brick, New Jersey, 08724
Principal Investigator: Evan Naylor

Hackensack University Medical Center
Hackensack, New Jersey, 07601
Principal Investigator: James McCloskey

Care Access Research Clifton
Clifton, New Jersey, 07013
Principal Investigator: Richards Afjonja

Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Principal Investigator: Dale Schaar

New Mexico

UNM
Albuquerque, New Mexico, 87102
Principal Investigator: Charles Foucar

New York

Clinical Research Alliance Research
Lake Success, New York, 11042
Principal Investigator: James D Olimpio

NYU Langone Long Island
Mineola, New York, 11501
Principal Investigator: Kiner-Strachan Bonnie

Manhattan Hematol Oncol Associates
New York, New York, 10016
Principal Investigator: Alec Goldenberg

SUNY Stony Brook Medical Oncology
Stony Brook, New York, 11794-8174
Principal Investigator: Michael A Schuster

SUNY Upstate Medical Center
Syracuse, New York, 13210
Principal Investigator: Teresa C Gentile

North Carolina

University of North Carolina Hospital
Chapel Hill, North Carolina,  27514
Principal Investigator: Josh Zeidner

Novant Health Heart and Vascular Institute
Charlotte, North Carolina, 28204
Principal Investigator: James Dugan

Duke University Medical Center
Durham, North Carolina, 27710
Principal Investigator: Lindsay Rein

Wake Forest University Health Sciences Oncology
Winston-Salem, North Carolina, 27157
Principal Investigator: Bayard L. Powell

Ohio

Hematology Oncology Care
Cincinnati, Ohio, 45236
Principal Investigator: Kruti Patel

Oregon

Oregon Health and Sciences University
Portland, Oregon, 97239
Principal Investigator: Michael Charles Heinrich

Texas

Texas Oncology P A TX Oncology Baylor
Dallas, Texas, 752521
Principal Investigator: Moshe Yair Levy

Houston Methodist Hospital
Houston, Texas, 77030
Principal Investigator: Shilpan Shah

University of TX MD Anderson Cancer Center
Houston, Texas, 77030
Principal Investigator: Koji Sasaki

Mays Cancer Center
San Antonio, Texas, 78229
Principal Investigator: Zohra Nooruddin

Utah

Community Cancer Trials of Utah
Ogden, Utah, 84405
Principal Investigator: Carl Gray

Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Principal Investigator: Srinivas Tantravahi

Virginia

Virginia Cancer Specialists
Gainesville, Virginia, 20155
Principal Investigator: Mitul Gandhi

Virginia Oncology Associates VOA – Lake Wright
Norfolk, Virginia, 23502
Principal Investigator: Robert Richard

Washington

VA Puget Sound Health Care System
Seattle, Wisconsin, 98108
Principal Investigator: Ehab Atallah

Wisconsin

Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Principal Investigator: Ehab Atallah