A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell

• Status: Not yet recruiting
• Trial end date: 2030-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class 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 is in a class of medications called tyrosine kinase inhibitors. It works 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 in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: 2-Aminopurine; Antibodies; Antibodies, Bispecific; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Asparaginase; Blinatumomab; Cortisone; Cyclophosphamide; Cytarabine; Dasatinib; Daunorubicin; Doxorubicin; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Immunoglobulins; Leucovorin; Liposomal doxorubicin; Mercaptopurine; Methotrexate; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Muromonab-CD3; Pegaspargase; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Thioguanine; Vincristine

Criteria

Inclusion Criteria:

• Patients must be > 365 days and < 18 years (for AIEOP-BFM), > 365 days and < 22 years (for COG) and > 365 days and < 46 years (for ALLTogether sites) at the time of enrollment

• Newly-diagnosed Ph+ or Ph-like ABL-class B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as those involving the following genes predicted to be sensitive to dasatinib: ABL1, ABL2, CSF1R, KIT, PDGFRA, and PDGFRB

• Evidence of ABL-class fusions including 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. 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., TruSight RNA Pan-Cancer Panel, Illumina, San Diego, CA, USA or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment

• Patients 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 have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vincristine

• Patients may have started dasatinib prior to study entry but cannot have received more than 14 days of dasatinib

• 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 (performed within 7 days prior to enrollment unless otherwise indicated):

• Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m^2

• 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) (within 7 days prior to enrollment unless otherwise indicated)

• Shortening fraction of ≥ 27% by echocardiogram or

• Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram AND

• Corrected QT Interval, QTc < 480mSec (within 7 days prior to enrollment unless otherwise indicated)

• Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment. (within 7 days prior to enrollment unless otherwise indicated)

Exclusion Criteria:

• Known history of chronic myeloid leukemia (CML)

• 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: Females of reproductive potential must use effective contraception during protocol treatment and for 30 days after the last dasatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer

• Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block

• Prior treatment with any TKI other than dasatinib

• 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 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

• Human immunodeficiency virus (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