The researchers are doing this study to find out whether PK-targeted fludarabine is an effective Lymphodepletion (LD) chemotherapy approach for people with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) who will receive tisagenlecleucel CAR T-cell therapy. The researchers will compare PK-targeted fludarabine dosing with standard fludarabine dosing to see which treatment approach is more effective. The researchers will also look at whether PK-targeted fludarabine dosing is feasible (practical), the side effects of the study treatment, and how the study treatment affects people's quality of life. The researchers will measure quality of life by having participants complete questionnaires.
Patients with B-ALL and eligible to receive commercial tisagenlecleucel.
Patient's weight > 9 kg at time of lymphodepleting chemotherapy
Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia
Hepatic: AST and ALT < 5x the upper limit of normal for age, unless thought to be leukemic disease-related
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including fludarabine, cyclophosphamide and tisagenlecleucel.
Patients with tisagenlecleucel that is deemed out of specification (OOS) will be excluded from this protocol
Clinically significant active and uncontrolled infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA etc.)
Patient/parent/guardian unable to give informed consent or unable to comply with the treatment protocol.
Parallel
Fludarabine
DrugFludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)
Cyclophosphamide
DrugAll patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).
Fludarabine
DrugTargeted fludarabine LD: Fludarabine 40 mg/m2/dose x 2 doses on days -6 and -5 (or -7 and -6), with doses on days -4 and -3 (or -5 and -4, if starting lymphodepletion on day -7) adjusted based on PK analysis to target a cumulative area under the curve (AUC) of 18 mg\*h/L (range 17.5-18.5mg\*h/L)
CAR-T
Biological/Vaccinewill be infused based on institutional guidelines.
compare the event free survival (EFS )
EFS is defined as time from randomization until non-response at day 28 after CAR T cell infusion, loss of B-cell aplasia \<6 months from the time of CAR T cell infusion, disease relapse, initiation of anti-leukemic therapy or death of any cause
survival
Click on the lead sponsor to view all of their trials.
Memorial Sloan Kettering Cancer Center
Lead sponsor
Princess Maxima Center for Pediatric Oncology
Collaborator
