Fludarabine dosing for children and young adults with B-cell acute lymphoblastic leukemia
Improving EveNt Free Survival by Optimizing FLUdarabine Exposure During LymphodepletioN for CAR T CEll Therapy: a Randomized, Multi-center Study of Children and Young Adults With B-cell Acute Lymphoblastic Leukemia (INFLUENCE)
This trial will test whether pharmacokinetic (PK)-targeted fludarabine dosing before tisagenlecleucel CAR T-cell therapy helps children and young adults with relapsed or refractory B‑cell ALL more than standard fludarabine dosing.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 130 (estimated) |
| Ages | 1 Year and up |
| Sex | All |
| Sponsor | Memorial Sloan Kettering Cancer Center Academic / other |
| Drugs / interventions | chemotherapy, cyclophosphamide, fludarabine, CAR T |
| Locations | 3 sites (New York, New York and 2 other locations) |
| Trial ID | NCT07223021 on ClinicalTrials.gov |
What this trial studies
This Phase 3 interventional study compares PK-targeted fludarabine dosing to standard fludarabine dosing as lymphodepletion prior to commercial tisagenlecleucel CAR T-cell therapy in children and young adults with relapsed/refractory B‑cell ALL. Participants who meet weight, organ function, and performance status requirements will receive lymphodepleting chemotherapy followed by CAR T infusion and will be followed for safety and efficacy outcomes. The study will measure feasibility of the PK-targeted approach, treatment side effects, and patient-reported quality of life using questionnaires. Enrollment and treatment are coordinated at Memorial Sloan Kettering Cancer Center with additional sites listed for data collection.
Who should consider this trial
Good fit: Children and young adults with relapsed or refractory B‑cell ALL who are eligible for commercial tisagenlecleucel, weigh more than 9 kg, and have adequate organ function and performance status are the ideal candidates.
Not a fit: Patients who are not eligible for tisagenlecleucel, weigh under 9 kg, or have inadequate organ function or performance status are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, PK-targeted fludarabine dosing could improve CAR T-cell effectiveness and reduce toxicity by personalizing drug exposure during lymphodepletion.
How similar studies have performed: Previous PK and transplant-associated studies indicate individualized fludarabine dosing can better achieve target exposures and may improve outcomes, but randomized data in the CAR T lymphodepletion setting remain limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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 μmol/L * Cardiac: LVEF ≥ 50% by multi-gated acquisition scan (MUGA), resting echocardiogram, or cardiac magnetic resonance imaging (MRI) within 6 weeks of screening * Pulmonary: Oxygen saturation as recorded by pulse oximetry of ≥ 90% on room air * Adequate performance status: * Age ≥ 16 years: ECOG ≤ 1 or Karnofsky \> 60% at treatment * Age \< 16 years: Lansky ≥ 60% at treatment * Willing to participate as research subject and provide written informed consent from parents/legal representative, patient, and age-appropriate assent as appropriate before any study specific screening procedures are conducted, according to local, regional or national law and legislation. Exclusion Criteria: * 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. * Pregnant or lactating women
Where this trial is running
New York, New York and 2 other locations
- Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
- Cincinnati Children's Hospital Medical Center (Data Collection Only) — Cincinnati, Ohio, United States (Recruiting)
- Children's Hospital of Philadelphia (Data Collection Only) — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Principal investigator: Kevin Curran, MD — Memorial Sloan Kettering Cancer Center
- Study coordinator: Kevin Curran, MD
- Email: currank@mskcc.org
- Phone: 1-833-MSK-KIDS
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.