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)
Biospecimen Collection: Undergo blood and CSF sample collection
Blinatumomab: Receive IV
Bone Marrow Biopsy: Undergo bone marrow biopsy
Calaspargase Pegol: Receive IV
Cyclophosphamide: Receive IV
Cytarabine: Receive IV or subcutaneously
Dasatinib: Receive PO
Daunorubicin: Receive IV
Doxorubicin: Receive IV
Echocardiography Test: Undergo ECHO
Imatinib: Given PO
Leucovorin: Receive PO or IV
Mercaptopurine: Receive PO
Methotrexate: Receive IT or IV or PO
Multigated Acquisition Scan: Undergo MUGA
Pegaspargase: Receive IV or intramuscularly
Prednisolone: Receive PO
Prednisone: Receive PO
Radiation Therapy: Undergo radiation therapy
Thioguanine: Receive PO
Vincristine: Receive IV
Study 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
Sex
ALL
Min age
366 Days
Max age
46 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Philadelphia chromosome-positive (Ph+) (BCR::ABL1-rearranged) 3-year event free survival (EFS) — Time from enrollment to first event, relapse, second malignancy, or death in complete remission, or last contact for those who are event-free, assessed up to 3 years Will be assessed in children, adolescents, and young adults \<25 years old with newly-diagnosed Ph+ (BCR::ABL1-rearranged) B acute lymphoblastic leukemia (B-ALL) who are treated with a modified Berlin-Frankfurt-Münster (mBFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib. Will be estimated using the Kaplan-Meier method with standard errors of Peto.
ABL-class Ph-like B-ALL 3-year event free survival (EFS) — Time from enrollment to first event, relapse, second malignancy, or death in complete remission, or last contact for those who are event-free, assessed up to 3 years Will be assessed in children, adolescents, and young adults \<25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without PDGFRB gene fusions. Will be estimated using the Kaplan-Meier method with standard errors of Peto.
Incidence of adverse events — Up to 3 years Will assess the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays \> 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous tyrosine kinase inhibitor (TKI). Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.
Trial sites (159)
Facility
City
Region
Status
Children's Hospital of Alabama
Birmingham
Alabama
Recruiting
Phoenix Childrens Hospital
Phoenix
Arizona
Recruiting
Banner University Medical Center - Tucson
Tucson
Arizona
Recruiting
Arkansas Children's Hospital
Little Rock
Arkansas
Recruiting
Kaiser Permanente Downey Medical Center
Downey
California
Recruiting
Loma Linda University Medical Center
Loma Linda
California
Recruiting
Miller Children's and Women's Hospital Long Beach
Long Beach
California
Recruiting
Children's Hospital Los Angeles
Los Angeles
California
Recruiting
Valley Children's Hospital
Madera
California
Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland
California
Recruiting
Kaiser Permanente-Oakland
Oakland
California
Recruiting
Children's Hospital of Orange County
Orange
California
Recruiting
Lucile Packard Children's Hospital Stanford University
Palo Alto
California
Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento
California
Recruiting
Rady Children's Hospital - San Diego
San Diego
California
Recruiting
UCSF Medical Center-Mission Bay
San Francisco
California
Recruiting
Children's Hospital Colorado
Aurora
Colorado
Recruiting
Connecticut Children's Medical Center
Hartford
Connecticut
Recruiting
Yale University
New Haven
Connecticut
Recruiting
Alfred I duPont Hospital for Children
Wilmington
Delaware
Recruiting
MedStar Georgetown University Hospital
Washington D.C.
District of Columbia
Recruiting
Children's National Medical Center
Washington D.C.
District of Columbia
Recruiting
Golisano Children's Hospital of Southwest Florida
Fort Myers
Florida
Recruiting
UF Health Cancer Institute - Gainesville
Gainesville
Florida
Recruiting
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood
Florida
Recruiting
Nemours Children's Clinic-Jacksonville
Jacksonville
Florida
Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
Florida
Recruiting
AdventHealth Orlando
Orlando
Florida
Recruiting
Arnold Palmer Hospital for Children
Orlando
Florida
Recruiting
Nemours Children's Hospital
Orlando
Florida
Recruiting
Nemours Children's Clinic - Pensacola
Pensacola
Florida
Recruiting
Johns Hopkins All Children's Hospital
St. Petersburg
Florida
Recruiting
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa
Florida
Recruiting
Saint Mary's Medical Center
West Palm Beach
Florida
Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta
Georgia
Recruiting
Augusta University Medical Center
Augusta
Georgia
Recruiting
Atrium Health Navicent
Macon
Georgia
Recruiting
Memorial Health University Medical Center
Savannah
Georgia
Recruiting
Kapiolani Medical Center for Women and Children
Honolulu
Hawaii
Recruiting
Saint Luke's Cancer Institute - Boise
Boise
Idaho
Recruiting
+ 119 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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