A Study of Fludarabine Dosing in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia

NCT07223021 | Recruiting Phase 3 FDA Drug

• 1 other identifier: 25-072
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Fludarabine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• survival

  2 years

Study Arms (2)

Standard Fludarabine regimen followed by CAR-T

ACTIVE COMPARATOR

Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CAR-T

Targeted fludarabine regimen followed by CAR-T

EXPERIMENTAL

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: Cyclophosphamide; Drug: Fludarabine; Biological: CAR-T

Interventions

Fludarabine DRUG

Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)

Standard Fludarabine regimen followed by CAR-T

CAR-T BIOLOGICAL

will be infused based on institutional guidelines.

Standard Fludarabine regimen followed by CAR-T; Targeted fludarabine regimen followed by CAR-T

Cyclophosphamide DRUG

All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).

Standard Fludarabine regimen followed by CAR-T; Targeted fludarabine regimen followed by CAR-T

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Princess Maxima Center for Pediatric Oncology: collaborator

Study Sites (3)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cincinnati Children's Hospital Medical Center (Data Collection Only)

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia (Data Collection Only)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Kevin Curran, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Curran, MD

CONTACT

1-833-MSK-KIDS; currank@mskcc.org

Jaap Jan Boelens, MD, PhD

CONTACT

1-833-MSK-KIDS

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomized open-label multicenter trial.

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: October 31, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (3)