Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 PositivePhase 2NCT03817398
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
A Phase 2 study testing Biospecimen Collection, Drug Withdrawn and Quality-of-Life Assessment in people with Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive, run by Children's Oncology Group at 173 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
- What is being tested?
- Biospecimen Collection, Drug Withdrawn and Quality-of-Life Assessment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 173 sitesin 4 countries
- Study dates
- 8 Nov 2019to 30 Sep 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
173 sites in 4 countries.
173 sites in 4 countries
United States157 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Tufts Children's Hospital
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
West Virginia University Charleston Division
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Missouri Children's Hospital
Columbia, Missouri, 65212
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Children's Hospital of Michigan
Detroit, Michigan, 48201
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Michigan State University
East Lansing, Michigan, 48823
El Paso Children's Hospital
El Paso, Texas, 79905
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
East Carolina University
Greenville, North Carolina, 27834
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
Norton Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Banner Children's at Desert
Mesa, Arizona, 85202
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
USA Health Strada Patient Care Center
Mobile, Alabama, 36604
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
NYP/Weill Cornell Medical Center
New York, New York, 10065
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Sacred Heart Hospital
Pensacola, Florida, 32504
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Renown Regional Medical Center
Reno, Nevada, 89502
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Carilion Children's
Roanoke, Virginia, 24014
University of Rochester
Rochester, New York, 14642
Corewell Health Children's
Royal Oak, Michigan, 48073
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
Memorial Health University Medical Center
Savannah, Georgia, 31404
Maine Children's Cancer Program
Scarborough, Maine, 04074
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Stony Brook University Medical Center
Stony Brook, New York, 11794
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Madigan Army Medical Center
Tacoma, Washington, 98431
Tampa General Hospital
Tampa, Florida, 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
New York Medical College
Valhalla, New York, 10595
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Medical Center
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Northwestern Medicine Central DuPage Hospital
Winfield, Illinois, 60190
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Canada10 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Children's Hospital
London, Ontario, N6A 5W9
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia5 sites
Monash Medical Center-Clayton Campus
Clayton, Victoria, 3168
John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales, 2310
Royal Children's Hospital
Parkville, Victoria, 3052
Perth Children's Hospital
Perth, Western Australia, 6009
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
Official title: Stopping Tyrosine Kinase Inhibitors (TKI) to Assess Treatment-Free Remission (TFR) in Pediatric Chronic Myeloid Leukemia - Chronic Phase (CML-CP)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- 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.
- Being tested
- Biospecimen Collection, Drug Withdrawn, Quality-of-Life Assessment, Questionnaire Administration, Tyrosine Kinase Inhibitor
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood collection
Drug WithdrawnOther
Also called discontinue (study treatment), Discontinued
Stop taking TKI medication
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Tyrosine Kinase InhibitorDrug
Also called Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK Inhibitors
Re-start TKI medication
| Study group | Role | What they receive |
|---|---|---|
| Basic Science (stop taking TKI, biospecimen collection) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Other: Drug Withdrawn; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tyrosine Kinase Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-free remission (TFR)
The Kaplan Meier method will be used to estimate 2-year TFR along with a 95% confidence interval.
Measured: From date of TKI discontinuation to the date of the first event (molecular recurrence, hematologic relapse, cytogenetic relapse, re-initiation of TKI therapy, second malignant neoplasm, or death) or censoring, assessed up to 2 years
Major molecular remission (MMR/MR3)
For patients re-initiating tyrosine kinase inhibitor (TKI) therapy, the cumulative incidence of major molecular remission will be calculated from the time of re-initiating TKI therapy treating deaths prior to achieving major molecular remission as competing events.
Measured: Up to 1 year
Secondary outcomes (1)
Clinical factors and laboratory correlates affecting persistence of MMR
Clinical factors and laboratory correlates (e.g. duration and level of prior molecular remission, risk score, duration and type of TKI, disease scoring system and immune studies etc.) affecting persistence of MMR and re-initiation of treatment after stopping TKI will be assessed by Cox proportional hazard regression models.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2019
- Study start8 Nov 2019
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sonali Chaudhury, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03817398
- Sponsor's protocol ID
- AAML18P1
- Other IDs
- NCI-2018-03439, AAML18P1, AAML18P1, U10CA180886
- Status last verified
- May 2026
- First submitted
- 2 Jan 2019
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No