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A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)

RecruitingPhase 2

An International Phase 2 Study of Chemotherapy and Tyrosine Kinase Inhibitors With Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or ABL-Class Philadelphia Chromosome-Like B-Cell Acute Lymphoblastic Leukemia

Who can join

366 Days – 46 Years · All sexes

Full eligibility criteria
Inclusion Criteria:

* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):

  * Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
  * Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR

  * Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
  * Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])

    * Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment

Exclusion Criteria:

* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding

  * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
  * Lactating females who plan to breastfeed their infants
  * Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol

    * NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement

  * Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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

About the study

This pilot trial assesses the effect of the combination of blinatumomab with dasatinib or imatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib and imatinib are in a class of medications called tyrosine kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib or imatinib in combination with standard chemotherapy may work better in treating patients with Ph+ or Ph-like ABL-class B-ALL than dasatinib or imatinib with chemotherapy.

What is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 222 · Started: May 30, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06124157

Locations in the U.S.

AlabamaChildren's Hospital of Alabama, Birmingham
ArizonaPhoenix Childrens Hospital, Phoenix
Banner University Medical Center - Tucson, Tucson
ArkansasArkansas Children's Hospital, Little Rock
CaliforniaKaiser Permanente Downey Medical Center, Downey
Loma Linda University Medical Center, Loma Linda
Miller Children's and Women's Hospital Long Beach, Long Beach
Children's Hospital Los Angeles, Los Angeles
Valley Children's Hospital, Madera
Kaiser Permanente-Oakland, Oakland
UCSF Benioff Children's Hospital Oakland, Oakland
Children's Hospital of Orange County, Orange
Lucile Packard Children's Hospital Stanford University, Palo Alto
University of California Davis Comprehensive Cancer Center, Sacramento
Rady Children's Hospital - San Diego, San Diego
UCSF Medical Center-Mission Bay, San Francisco
ColoradoChildren's Hospital Colorado, Aurora
ConnecticutConnecticut Children's Medical Center, Hartford
Yale University, New Haven
DelawareAlfred I duPont Hospital for Children, Wilmington
District of ColumbiaChildren's National Medical Center, Washington D.C.
MedStar Georgetown University Hospital, Washington D.C.
FloridaGolisano Children's Hospital of Southwest Florida, Fort Myers
UF Health Cancer Institute - Gainesville, Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Nemours Children's Clinic-Jacksonville, Jacksonville
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami
AdventHealth Orlando, Orlando
Arnold Palmer Hospital for Children, Orlando
Nemours Children's Hospital, Orlando
Nemours Children's Clinic - Pensacola, Pensacola
Johns Hopkins All Children's Hospital, St. Petersburg
Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa
Saint Mary's Medical Center, West Palm Beach
GeorgiaChildren's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta
Augusta University Medical Center, Augusta
Atrium Health Navicent, Macon
Memorial Health University Medical Center, Savannah
HawaiiKapiolani Medical Center for Women and Children, Honolulu
IdahoSaint Luke's Cancer Institute - Boise, Boise
IllinoisLurie Children's Hospital-Chicago, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
University of Illinois, Chicago
Advocate Children's Hospital-Oak Lawn, Oak Lawn
Advocate Children's Hospital-Park Ridge, Park Ridge
OSF Children's Hospital of Illinois, Peoria
Southern Illinois University School of Medicine, Springfield
IndianaRiley Hospital for Children, Indianapolis
IowaBlank Children's Hospital, Des Moines
University of Iowa/Holden Comprehensive Cancer Center, Iowa City
KentuckyUniversity of Kentucky/Markey Cancer Center, Lexington
Norton Children's Hospital, Louisville
LouisianaChildren's Hospital New Orleans, New Orleans
Ochsner Medical Center Jefferson, New Orleans
MaineMaine Children's Cancer Program, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
Sinai Hospital of Baltimore, Baltimore
Walter Reed National Military Medical Center, Bethesda
MassachusettsDana-Farber Cancer Institute, Boston
UMass Memorial Medical Center - University Campus, Worcester
MichiganC S Mott Children's Hospital, Ann Arbor
Children's Hospital of Michigan, Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids
Bronson Methodist Hospital, Kalamazoo
MinnesotaChildren's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis
University of Minnesota/Masonic Cancer Center, Minneapolis
Mayo Clinic in Rochester, Rochester
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriChildren's Mercy Hospitals and Clinics, Kansas City
Washington University School of Medicine, St Louis
NebraskaChildren's Hospital and Medical Center of Omaha, Omaha
NevadaAlliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New JerseyHackensack University Medical Center, Hackensack
Morristown Medical Center, Morristown
Jersey Shore Medical Center, Neptune City
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick
Saint Joseph's Regional Medical Center, Paterson
New MexicoPresbyterian Hospital, Albuquerque
University of New Mexico Cancer Center, Albuquerque
New YorkAlbany Medical Center, Albany
Roswell Park Cancer Institute, Buffalo
NYU Langone Hospital - Long Island, Mineola
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
Memorial Sloan Kettering Cancer Center, New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York
NYP/Weill Cornell Medical Center, New York
Stony Brook University Medical Center, Stony Brook
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
New York Medical College, Valhalla
North CarolinaMission Hospital, Asheville
UNC Lineberger Comprehensive Cancer Center, Chapel Hill
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Duke University Medical Center, Durham
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Broadway Medical Center, Fargo
OhioChildren's Hospital Medical Center of Akron, Akron
Cincinnati Children's Hospital Medical Center, Cincinnati
Rainbow Babies and Childrens Hospital, Cleveland
Nationwide Children's Hospital, Columbus
Dayton Children's Hospital, Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
PennsylvaniaLehigh Valley Hospital-Cedar Crest, Allentown
Penn State Children's Hospital, Hershey
Children's Hospital of Philadelphia, Philadelphia
Saint Christopher's Hospital for Children, Philadelphia
Children's Hospital of Pittsburgh of UPMC, Pittsburgh
Rhode IslandRhode Island Hospital, Providence
South CarolinaPrisma Health Richland Hospital, Columbia
BI-LO Charities Children's Cancer Center, Greenville
South DakotaSanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeEast Tennessee Childrens Hospital, Knoxville
The Children's Hospital at TriStar Centennial, Nashville
Vanderbilt University/Ingram Cancer Center, Nashville
TexasDell Children's Medical Center of Central Texas, Austin
Driscoll Children's Hospital, Corpus Christi
Medical City Dallas Hospital, Dallas
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
El Paso Children's Hospital, El Paso
Cook Children's Medical Center, Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston
Covenant Children's Hospital, Lubbock
UMC Cancer Center / UMC Health System, Lubbock
Children's Hospital of San Antonio, San Antonio
Methodist Children's Hospital of South Texas, San Antonio
University of Texas Health Science Center at San Antonio, San Antonio
Scott and White Memorial Hospital, Temple
UtahPrimary Children's Hospital, Salt Lake City
VermontUniversity of Vermont and State Agricultural College, Burlington
VirginiaUniversity of Virginia Cancer Center, Charlottesville
Inova Fairfax Hospital, Falls Church
Children's Hospital of The King's Daughters, Norfolk
VCU Massey Comprehensive Cancer Center, Richmond
Carilion Children's, Roanoke
WashingtonSeattle Children's Hospital, Seattle
Providence Sacred Heart Medical Center and Children's Hospital, Spokane
Mary Bridge Children's Hospital and Health Center, Tacoma
WisconsinSaint Vincent Hospital Cancer Center Green Bay, Green Bay
University of Wisconsin Carbone Cancer Center - University Hospital, Madison
Children's Hospital of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.