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

NCT ID: NCT07223021

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-20
• Study Completion Date: 2028-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Fludarabine regimen followed by CAR-T

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

Group Type: ACTIVE_COMPARATOR

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

CAR-T

Intervention Type: BIOLOGICAL

will be infused based on institutional guidelines.

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

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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)

CAR-T

Intervention Type: BIOLOGICAL

will be infused based on institutional guidelines.

Interventions

Fludarabine

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: 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)

Intervention Type: DRUG

CAR-T

will be infused based on institutional guidelines.

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Princess Maxima Center for Pediatric Oncology

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Curran, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kevin Curran, MD

Role: CONTACT

currank@mskcc.org

1-833-MSK-KIDS

Jaap Jan Boelens, MD, PhD

Role: CONTACT

1-833-MSK-KIDS

Facility Contacts

Kevin Curran, MD

Role: primary

1-833-MSK-KIDS

Jaap Jan Boelens, MD,PhD

Role: backup

1-833-MSK-KIDS

Related Links

https://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

25-072

Identifier Type: -

Identifier Source: org_study_id