Optimizing fludarabine phosphate exposure to improve event‑free survival in children and young adults with B‑cell acute lymphoblastic leukemia receiving CAR‑T therapy

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What is this study about?

The study focuses on children and young adults who have B-cell Acute Lymphoblastic Leukemia that has returned after previous treatment or did not respond to it. Participants receive a medication called fludarabine before being given CAR T cell therapy, a treatment where a patient’s own immune cells are engineered to attack the cancer. The main aim of the trial is to compare the EFS between patients who receive the usual dose of fludarabine and those whose dose is adjusted to reach a specific drug level.

After giving consent, participants are randomly assigned to either the standard fludarabine dosing group or the target‑level dosing group. All patients then undergo the CAR T cell infusion and are followed for several months to monitor how long they remain free of disease progression, need for new leukemia treatment, or other serious complications. Visits include routine check‑ups, blood tests, and simple questionnaires about how they feel, allowing researchers to see whether the adjusted dosing improves outcomes and safety.

1 join the trial

after consent, you become a participant in the influence trial. the trial aims to improve car t cell therapy for children and young adults with b‑cell acute lymphoblastic leukemia.

2 randomization

the study assigns you to one of two groups: standard fludarabine exposure or targeted fludarabine exposure. this assignment is done by a computer system and you do not choose the group.

3 baseline assessments

before any treatment, you will undergo a series of tests. these include blood work, bone‑marrow examination, and other evaluations to confirm disease status and organ function.

the results are used to ensure it is safe for you to receive the study medications and the later car t cell infusion.

4 fludarabine administration

you will receive fludarabine phosphate as an intravenous (iv) infusion. the dose is 40 mg per square meter of body‑surface area (mg/m2).

the medication is given through a vein over a short period, according to the trial schedule. the purpose is to reduce (lymphodeplete) certain immune cells so that the later car t cells can expand effectively.

the exact number of days of fludarabine dosing follows the protocol and is the same for all participants in your assigned group.

5 car t cell infusion

after fludarabine, you will receive the engineered car t cells by iv infusion. this is a single infusion administered in the hospital.

the infusion marks day 0 of post‑infusion monitoring.

6 early monitoring (day 0‑28)

for the first four weeks after the infusion, you will stay in the hospital or return frequently for observation.

medical staff will check for signs of response, side effects such as cytokine release syndrome (crs) or neurotoxicity (icans), blood counts, and infections.

7 assessment at day 28

on day 28, a formal evaluation is performed to determine whether you have achieved a response.

the assessment includes blood and bone‑marrow tests to see if leukemia cells are absent and whether b‑cell aplasia (absence of normal b cells) is present.

8 ongoing monitoring (day 28‑180)

for the next five months, you will have regular visits to monitor for late side effects, including severe cytopenia (low blood cell counts) and infections.

the study records the duration of b‑cell aplasia, the number of circulating car t cells, and any serious adverse events.

9 long‑term follow‑up (up to 2 years)

after the 180‑day period, follow‑up visits continue for up to two years.

these visits assess disease relapse, need for additional anti‑leukemic therapy, overall survival, and patient‑reported outcomes.

blood tests and clinical evaluations are performed at scheduled intervals, including a check at one year for b‑cell aplasia and car t cell persistence.

Who Can Join the Study?

Have B-cell acute lymphoblastic leukemia (B-ALL) and be eligible to receive the CAR T‑cell therapy called tisagenlecleucel.
Weigh more than 9 kg (about 20 lb) at the time of screening.
Have healthy liver function, which means:
- Blood level of bilirubin (a substance processed by the liver) is 2 mg/dL or lower, unless you have a known harmless condition that raises it.
- Liver enzymes called AST and ALT are less than five times the normal range for your age, unless the rise is caused by the leukemia.
Have healthy kidney function, measured by a glomerular filtration rate (GFR) of at least 70 ml/min/1.73 m², which shows how well the kidneys filter waste.
Have healthy heart function, shown by a left ventricular ejection fraction (LVEF) of 50 % or higher on a heart scan (MUGA), ultrasound (echocardiogram) or MRI performed within the past 6 weeks. LVEF indicates how well the heart pumps blood.
Have adequate lung function, meaning an oxygen saturation of 90 % or higher on normal air, measured with a fingertip device called pulse oximetry.
Have a good overall activity level (performance status):
- If you are 16 years or older: an ECOG score of 0‑1 (fully active or able to do light work) or a Karnofsky score above 60 % (you can care for yourself).
- If you are younger than 16 years: a Lansky score above 60 % (you can handle most daily activities).
Be willing to join the research and sign the required forms, including written consent from a parent or legal guardian and, when appropriate, your own agreement (assent) as required by local law.
Be within the age range the study includes, which covers children and young adults (generally starting around 2 years old).

Who Cannot Join the Study?

Having a known immediate or delayed allergic (hypersensitivity) reaction or unusual response (idiosyncrasy) to any of the study medicines, including fludarabine, cyclophosphamide, the cell therapy called tisagenlecleucel, or to similar ingredients.
Receiving a dose of tisagenlecleucel that does not meet the required quality standards (called out of specification (OOS)), which means the product is not suitable for the trial.
Having a serious, active infection that is not under control, proven by symptoms, imaging tests, or laboratory results such as blood cultures or a genetic test called PCR (which looks for DNA or RNA of germs).
Being unable to give or have a parent/guardian give informed consent (the agreement to join the study after understanding it) or being unable to follow the study’s treatment schedule.
Being pregnant or lactating (breast‑feeding), because the study medicines could affect the baby.
Having another uncontrolled or symptomatic illness that could interfere with the study, such as an ongoing infection, a severe mental health condition (psychiatric illness), or social situations that would make it hard to follow the study rules, and which the study doctor (PI, principal investigator) believes would be unsafe.

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country
Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht	The Netherlands
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
Uwijidtuajgxavqsyjahz Mwhlnleu Aot	Munster	Germany

Trial status

Country	Status	Recruitment Start
Germany	Not yet recruiting	01.04.2026
Spain	Not yet recruiting	01.04.2026
The Netherlands	Not yet recruiting	01.04.2026

Trial locations

Investigated drugs:

Fludarabine Phosphate

Fludarabine phosphate is a chemotherapy medicine given through a vein. In this study it is used before the main treatment to lower the number of immune cells (lymphodepletion). Lowering these cells helps the later therapy work better. The trial is testing whether giving a standard amount or a dose that is adjusted specifically for each patient leads to better outcomes.

CAR T cell therapy is a type of treatment that uses a patient’s own immune cells, which are taken out, changed in a lab to recognize and attack cancer cells, and then put back into the body. In this trial the CAR T cells are designed to target B‑cell acute lymphoblastic leukemia. The goal is to see how the different fludarabine dosing strategies affect the success of this cellular therapy.

B-cell Acute Lymphoblastic Leukemia – B-cell acute lymphoblastic leukemia is a fast‑growing cancer that starts in the bone marrow where immature B‑cell precursors develop. The disease causes an abnormal rise of these early B‑cells, called blasts, which crowd out normal blood cells. As the number of blasts increases, patients may develop low blood counts, leading to easy bruising, fatigue, or infections. The abnormal cells can also move into the bloodstream and spread to other organs such as the brain or spinal fluid. Over time, the disease can worsen as more of the marrow is taken over, reducing the body’s ability to make healthy blood cells.

Trial ID:

2025-523096-34-00

Protocol code:

INFLUENCE

NCT ID:

NCT07223021

Trial Phase:

Therapeutic confirmatory (Phase III)

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Optimizing fludarabine phosphate exposure to improve event‑free survival in children and young adults with B‑cell acute lymphoblastic leukemia receiving CAR‑T therapy

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?