Recruiting
Phase 3

PK-Targeted Fludarabine vs. Fludarabine

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT07223021

Conditions

B-cell Acute Lymphoblastic Leukemia

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

Interventions

Fludarabine

Cyclophosphamide

Fludarabine

CAR-T

Study Details

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 ID

NCT07223021

Start date

Oct 20, 2025

Status verified date

Aug, 2026

Completion date

Oct, 2028

Anticipated

Primary completion date

Oct, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

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 Design

Enrollment

65 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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)

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

Interventions

Fludarabine

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

Cyclophosphamide

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

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)

CAR-T

will be infused based on institutional guidelines.

Primary outcome measure

  • compare the event free survival (EFS ) [ Time Frame: 28 days ]

Central Contacts and Locations

Central contacts

Kevin Curran, MD

1-833-MSK-KIDScurrank@mskcc.org

Jaap Jan Boelens, MD, PhD

1-833-MSK-KIDS

Locations

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Kevin Curran, MD

1-833-MSK-KIDS

Jaap Jan Boelens, MD,PhD

1-833-MSK-KIDS

Principal Investigator:

Kevin Curran, MD

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

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Christine Phillips, MD

513-636-4266

Children's Hospital of Philadelphia (Data Collection Only)

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Regina Myers, MD

267-426-0762

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Keywords

  • Fludarabine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-08-17.