B-cell Acute Lymphoblastic LeukemiaPhase 3NCT07223021
A Study of Fludarabine Dosing in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia
A Phase 3 study testing Fludarabine, Cyclophosphamide and CAR-T in people with B-cell Acute Lymphoblastic Leukemia, run by Memorial Sloan Kettering Cancer Center at 6 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- Fludarabine, Cyclophosphamide and CAR-T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 20 Oct 2025to Oct 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Trial locations and contacts
6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Jaap Jan Boelens, MD, PhD contact
6 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center (Data Collection Only)
Cincinnati, Ohio, 45229
Christine Phillips, MD, 513-636-4266
- Not yet recruiting
Baylor College Medical Center (Data Collection Only)
Houston, Texas, 77030
Rayne Rouce, MD, rouce@bcm.edu
- Recruiting
Texas Children's Hospital (Data Collection)
Houston, Texas, 77030
Rayne Rouce, M.D., B.S., 832-822-4242
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Kevin Curran, MD, 1-833-MSK-KIDS
Jaap Jan Boelens, MD,PhD, 1-833-MSK-KIDS
- Recruiting
Children's Hospital of Philadelphia (Data Collection Only)
Philadelphia, Pennsylvania, 19104
Regina Myers, MD, 267-426-0762
Netherlands1 site, 1 recruiting
- Recruiting
Prinses Máxima Centrum (Data Collection and Analysis)
Utrecht
Friso Calkoen, MD, +31 88 972 7272
About this study
Official title: 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.
- Conditions
- B-cell Acute Lymphoblastic Leukemia
- Being tested
- Fludarabine, Cyclophosphamide, CAR-T
- Keywords
- Fludarabine
- Medical subject headings
- Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)
CyclophosphamideDrug
All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).
FludarabineDrug
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-TBiological
will be infused based on institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: CAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
Secondary outcomes (1)
survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2025
- Study start20 Oct 2025
- Primary completionOct 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is a randomized open-label multicenter trial.
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Maxima Center for Pediatric Oncology
- Responsible party
- Sponsor
- Investigators
- Kevin Curran, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07223021
- Sponsor's protocol ID
- 25-072
- Status last verified
- Oct 2026
- First submitted
- 28 Oct 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.