An International Pilot 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

Status: Recruiting
Location: See all (117) locations...
Intervention Type: Drug, Procedure, Biological, Radiation
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 46
Healthy Volunteers: f
View:

• 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

Locations
United States
Alabama
Children's Hospital of Alabama
RECRUITING
Birmingham
Arkansas
Arkansas Children's Hospital
RECRUITING
Little Rock
Arizona
Phoenix Childrens Hospital
RECRUITING
Phoenix
California
Loma Linda University Medical Center
RECRUITING
Loma Linda
Miller Children's and Women's Hospital Long Beach
RECRUITING
Long Beach
Kaiser Permanente-Oakland
RECRUITING
Oakland
UCSF Benioff Children's Hospital Oakland
RECRUITING
Oakland
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
RECRUITING
Palo Alto
Rady Children's Hospital - San Diego
RECRUITING
San Diego
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Connecticut
Yale University
RECRUITING
New Haven
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington D.c.
MedStar Georgetown University Hospital
RECRUITING
Washington D.c.
Delaware
Alfred I duPont Hospital for Children
RECRUITING
Wilmington
Florida
Golisano Children's Hospital of Southwest Florida
RECRUITING
Fort Myers
UF Health Cancer Institute - Gainesville
RECRUITING
Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
RECRUITING
Hollywood
Nemours Children's Clinic-Jacksonville
RECRUITING
Jacksonville
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
Arnold Palmer Hospital for Children
RECRUITING
Orlando
Nemours Children's Clinic - Pensacola
RECRUITING
Pensacola
Johns Hopkins All Children's Hospital
RECRUITING
St. Petersburg
Georgia
Augusta University Medical Center
RECRUITING
Augusta
Atrium Health Navicent
RECRUITING
Macon
Memorial Health University Medical Center
RECRUITING
Savannah
Hawaii
Kapiolani Medical Center for Women and Children
RECRUITING
Honolulu
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Illinois
Lurie Children's Hospital-Chicago
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Advocate Children's Hospital-Oak Lawn
RECRUITING
Oak Lawn
Advocate Children's Hospital-Park Ridge
RECRUITING
Park Ridge
Southern Illinois University School of Medicine
RECRUITING
Springfield
Indiana
Riley Hospital for Children
RECRUITING
Indianapolis
Kentucky
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Louisiana
Ochsner Medical Center Jefferson
RECRUITING
New Orleans
Massachusetts
UMass Memorial Medical Center - University Campus
RECRUITING
Worcester
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Sinai Hospital of Baltimore
RECRUITING
Baltimore
Walter Reed National Military Medical Center
RECRUITING
Bethesda
Maine
Maine Children's Cancer Program
RECRUITING
Scarborough
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Children's Hospital of Michigan
RECRUITING
Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITING
Grand Rapids
Bronson Methodist Hospital
RECRUITING
Kalamazoo
Minnesota
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
Children's Mercy Hospitals and Clinics
RECRUITING
Kansas City
Washington University School of Medicine
RECRUITING
St Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
North Carolina
Mission Hospital
RECRUITING
Asheville
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Duke University Medical Center
RECRUITING
Durham
Wake Forest University Health Sciences
RECRUITING
Winston-salem
Nebraska
Children's Hospital and Medical Center of Omaha
RECRUITING
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
RECRUITING
Lebanon
New Jersey
Morristown Medical Center
RECRUITING
Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
Saint Joseph's Regional Medical Center
RECRUITING
Paterson
Nevada
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
RECRUITING
Las Vegas
New York
Albany Medical Center
RECRUITING
Albany
Roswell Park Cancer Institute
RECRUITING
Buffalo
NYU Langone Hospital - Long Island
RECRUITING
Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Stony Brook University Medical Center
RECRUITING
Stony Brook
State University of New York Upstate Medical University
RECRUITING
Syracuse
New York Medical College
RECRUITING
Valhalla
Ohio
Children's Hospital Medical Center of Akron
RECRUITING
Akron
Cincinnati Children's Hospital Medical Center
RECRUITING
Cincinnati
Rainbow Babies and Childrens Hospital
RECRUITING
Cleveland
Dayton Children's Hospital
RECRUITING
Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
RECRUITING
Toledo
Pennsylvania
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Saint Christopher's Hospital for Children
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
South Carolina
Prisma Health Richland Hospital
RECRUITING
Columbia
BI-LO Charities Children's Cancer Center
RECRUITING
Greenville
Tennessee
East Tennessee Childrens Hospital
RECRUITING
Knoxville
The Children's Hospital at TriStar Centennial
RECRUITING
Nashville
Vanderbilt University/Ingram Cancer Center
RECRUITING
Nashville
Texas
Dell Children's Medical Center of Central Texas
RECRUITING
Austin
Driscoll Children's Hospital
RECRUITING
Corpus Christi
Medical City Dallas Hospital
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
El Paso Children's Hospital
RECRUITING
El Paso
Cook Children's Medical Center
RECRUITING
Fort Worth
Covenant Children's Hospital
RECRUITING
Lubbock
UMC Cancer Center / UMC Health System
RECRUITING
Lubbock
Children's Hospital of San Antonio
RECRUITING
San Antonio
Methodist Children's Hospital of South Texas
RECRUITING
San Antonio
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Primary Children's Hospital
RECRUITING
Salt Lake City
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Inova Fairfax Hospital
RECRUITING
Falls Church
Children's Hospital of The King's Daughters
RECRUITING
Norfolk
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Vermont
University of Vermont and State Agricultural College
RECRUITING
Burlington
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
RECRUITING
Spokane
Mary Bridge Children's Hospital and Health Center
RECRUITING
Tacoma
Wisconsin
Saint Vincent Hospital Cancer Center Green Bay
RECRUITING
Green Bay
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Children's Hospital of Wisconsin
RECRUITING
Milwaukee
Other Locations
Australia
Perth Children's Hospital
RECRUITING
Perth
Canada
IWK Health Centre
RECRUITING
Halifax
McMaster Children's Hospital at Hamilton Health Sciences
RECRUITING
Hamilton
Centre Hospitalier Universitaire Sainte-Justine
RECRUITING
Montreal
The Montreal Children's Hospital of the MUHC
RECRUITING
Montreal
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
RECRUITING
Québec
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
RECRUITING
Sherbrooke
Hospital for Sick Children
RECRUITING
Toronto
British Columbia Children's Hospital
RECRUITING
Vancouver
Puerto Rico
University Pediatric Hospital
RECRUITING
San Juan
Time Frame
Start Date: 2025-05-30
Estimated Completion Date: 2030-12-01
Participants
Target number of participants: 222
Treatments
Experimental: Stratum I (Ph+ ALL)
See detailed description
Experimental: Stratum II (PDGFRB ABL-Class fusions)
See detailed description.
Experimental: Stratum III (non-PDGFRB ABL-Class fusions)
See detailed description.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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