Memorial Sloan Kettering Cancer Center
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.
Inclusion Criteria: * Patients with B-ALL and eligible to receive commercial tisagenlecleucel. * Patient's weight \> 9 kg at time of lymphodepleting chemotherapy * Adequate organ function at time of LD is required and is defined: * 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 * Renal: Calculated glomerular filtration rate (GFR) ≥ 70 ml/min/1.73m\^2. (based on Schwartz formula GFR (mL/min/1.73 m²) = (36.2 × Height in cm) / Creatinine in mg/dL…
Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)
All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).
Targeted 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)
will be infused based on institutional guidelines.