Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia

NCT ID: NCT03817398

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-08

Study Completion Date

2026-06-30

Brief Summary

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This phase II trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the 2-year treatment free remission (TFR) rate of children, adolescents, and young adults with chronic myeloid leukemia - chronic phase (CML-CP) following discontinuation tyrosine kinase inhibitor (TKI).

II. To estimate the re-induction rate and maintenance of molecular remission (BCR-ABL1 =\< 0.1%) at 1 year after restarting TKI for children, adolescents, and young adults.

SECONDARY OBJECTIVE:

I. To describe clinical factors and laboratory correlates affecting the persistence of major molecular remission (MMR) and re-initiation of treatment after stopping TKI (e.g. patient demographics, duration and level of prior molecular remission, duration and type of TKI, clinical presentation at diagnosis and immune studies).

EXPLORATORY OBJECTIVES:

I. To describe change in height standard deviation score over time in patients who are able to discontinue their TKI.

II. To describe the long-term health outcomes including but not limited to gonadal function, endocrine function, and bone metabolism in patients who are able to discontinue TKI as well as those that need to restart TKIs.

III. To describe differences in patient-reported health status after stopping TKIs, including those who need to resume TKI after stopping.

IV. To describe the incidence and characteristics of TKI withdrawal syndrome in children.

V. To evaluate changes in neurocognitive outcomes of patients enrolled on this study using a patient-completed, performance-based, computerized measure of neuropsychological functioning and a parent-report/self-report questionnaire.

OUTLINE:

Patients stop taking TKI medication within 10 days after enrollment. Patients undergo peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3. Patients who lose their molecular remission may restart TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3.

After completion of study treatment, patients are followed up annually.

Conditions

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Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Basic Science (stop taking TKI, biospecimen collection)

Patients stop taking TKI medication within 10 days after enrollment. Patients undergo peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3. Patients who lose their molecular remission may restart TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood collection

Drug Withdrawn

Intervention Type OTHER

Stop taking TKI medication

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Tyrosine Kinase Inhibitor

Intervention Type DRUG

Re-start TKI medication

Interventions

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Biospecimen Collection

Undergo blood collection

Intervention Type PROCEDURE

Drug Withdrawn

Stop taking TKI medication

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Tyrosine Kinase Inhibitor

Re-start TKI medication

Intervention Type DRUG

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection discontinue (study treatment) Discontinued Quality of Life Assessment Protein Tyrosine Kinase Inhibitors PTK Inhibitors TK Inhibitors

Eligibility Criteria

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Inclusion Criteria

* Patient must have been diagnosed with CML-CP at \< 18 years of age.
* Patient must have histologic verification of CML-CP at original diagnosis
* Patient must be in molecular remission (MR) with a BCR-ABL1 level of =\< 0.01% BCR-ABL1 as measured using the International Scale (IS) by RQ-PCR for \>= 2 consecutive years at the time of enrollment

* Please note: The lab evaluating disease status and molecular response for this study must be College of American Pathology (CAP) and/or Clinical Laboratory Improvement Amendments (CLIA) certified (United States \[US\] only), sites in other countries must be certified by their accredited authorities. All labs must use the International Scale guidelines with a sensitivity of detection assay =\< 0.01% BCR-ABL1 and be able to report results in =\< 2 weeks
* Patient must have received any TKI for a minimum of 3 consecutive years at time of enrollment
* Patient agrees to discontinue TKI therapy
* REGULATORY REQUIREMENTS
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
* ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
* Age \>= 8 years at the time of enrollment
* Ability to understand English or Spanish
* Cognitive ability to complete instruments according to the primary team
* ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
* Patient must be 5 years or older at the time of enrollment
* English-, French- or Spanish-speaking
* No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down syndrome, Fragile X, William syndrome, mental retardation)
* No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli

Exclusion Criteria

* Known T3151 mutation
* Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive (+) cells at any time prior to enrollment that include "major route" abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or abnormalities of 3q26.2
* History of accelerated phase or blast crisis CML
* Female patients who are pregnant
* Lactating females are not eligible unless they have agreed not to breastfeed their infants
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sonali Chaudhury

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Site Status

Banner Children's at Desert

Mesa, Arizona, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Site Status

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Northwestern Medicine Central DuPage Hospital

Winfield, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Tufts Children's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Michigan State University

East Lansing, Michigan, United States

Site Status

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

Corewell Health Children's

Royal Oak, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri Children's Hospital

Columbia, Missouri, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Renown Regional Medical Center

Reno, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

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State University of New York Upstate Medical University

Syracuse, New York, United States

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Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

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New York Medical College

Valhalla, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

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UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center-Amarillo

Amarillo, Texas, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

El Paso Children's Hospital

El Paso, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

UMC Cancer Center / UMC Health System

Lubbock, Texas, United States

Site Status

Children's Hospital of San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Site Status

Carilion Children's

Roanoke, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

West Virginia University Charleston Division

Charleston, West Virginia, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Site Status

John Hunter Children's Hospital

Hunter Regional Mail Centre, New South Wales, Australia

Site Status

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status

Monash Medical Center-Clayton Campus

Clayton, Victoria, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Perth Children's Hospital

Perth, Western Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Children's Hospital

London, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, , Canada

Site Status

HIMA San Pablo Oncologic Hospital

Caguas, , Puerto Rico

Site Status

Countries

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United States Australia Canada Puerto Rico

Other Identifiers

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NCI-2018-03439

Identifier Type: REGISTRY

Identifier Source: secondary_id

AAML18P1

Identifier Type: OTHER

Identifier Source: secondary_id

AAML18P1

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAML18P1

Identifier Type: -

Identifier Source: org_study_id