A Study of Fludarabine Dosing in 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)

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.

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kevin Curran, MD; Phone Number: 1-833-MSK-KIDS; Email: currank@mskcc.org
• Study Contact Backup: Name: Jaap Jan Boelens, MD, PhD; Phone Number: 1-833-MSK-KIDS

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Kevin Curran, MD
      • Contact: Kevin Curran, MD; Phone Number: 1-833-MSK-KIDS
      • Contact: Jaap Jan Boelens, MD,PhD; Phone Number: 1-833-MSK-KIDS
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center (Data Collection Only)
      • Contact: Christine Phillips, MD; Phone Number: 513-636-4266
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia (Data Collection Only)
      • Contact: Regina Myers, MD; Phone Number: 267-426-0762
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Texas Children's Hospital (Data Collection)
      • Contact: Rayne Rouce, M.D., B.S.; Phone Number: 832-822-4242
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Baylor College Medical Center (Data Collection Only)
      • Contact: Rayne Rouce, MD; Email: rouce@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Fludarabine regimen followed by CAR-T; Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)	Drug: Fludarabine; Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4); Drug: Cyclophosphamide; All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).; Drug: Fludarabine; 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); Biological: CAR-T; will be infused based on institutional guidelines.
Experimental: Targeted fludarabine regimen followed by CAR-T; 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	Drug: Fludarabine; Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4); Drug: Cyclophosphamide; All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).; Drug: Fludarabine; 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); Biological: CAR-T; will be infused based on institutional guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
survival	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Princess Maxima Center for Pediatric Oncology
• Investigators: Principal Investigator: Kevin Curran, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: October 28, 2025
• First Posted (Actual): October 31, 2025

Study Record Updates

• Last Update Posted (Actual): August 17, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Fludarabine
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Burkitt Lymphoma; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: 25-072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No