The INFLUENCE Trial: Improve CAR T cell therapy by optimizing fludarabine exposure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2025-523096-34-00

ClinicalTrials.gov

NCT07223021

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic

To compare the EFS in patients receiving standard versus targeted fludarabine LD prior to CAR T cell infusion in pediatric/young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).

Secondary objectives 10

1. Estimate the one- and two- year overall survival in both arms and compare overall survival.
2. Estimate and compare the percentage of non-response at Day 28 post CAR T cell therapy between the two arms.
3. Estimate and compare the percentage of cumulative incidence of disease relapse.
4. Estimate and compare the percentage of patients who initiate any anti-leukemia therapy, including allogeneic hematopoietic stem cell transplant (allo-HCT).
5. Characterize and compare the post CAR T cell toxicity in both arms including adverse events of special interest (AESI; cytokine release syndrome (CRS), immune cell associated neurotoxicity syndrome (ICANS) , grade 3-4 cytopenia from day 28 – day 180, and infectious adverse events (grade 3-5) during the first 180 days after CAR T cell infusion)
6. Compare the persistence of CAR T cells post infusion in both arms.
7. Compare the duration of peripheral blood BCA in both arms
8. Estimate and compare the percentage of patients who develop bone marrow B-cell recovery (≥1% CD19+ normal B-cells in the bone marrow) within 6 months after CAR-T infusion
9. Assess the feasibility of achieving targeted fludarabine exposure (AUC 18 mg*h/L) by TDM and compare to standard fludarabine conditioning.
10. Determine the quality of life (QoL) by patient reported outcomes (PROs)

Conditions and MedDRA coding

B-cell Acute Lymphoblastic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients with B-ALL and eligible to receive commercial tisagenlecleucel.
2. Patient’s weight >9kg at time of screening
3. 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/1.73m2. (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
4. Adequate performance status: Age ≥16 years: ECOG ≤1 or Karnofsky >60% at screening, Age <16 years: Lansky >60% at screening
5. 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 6

1. 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.
2. Patients with tisagenlecleucel that is deemed out of specification (OOS) will be excluded from this protocol
3. Clinically significant active and uncontrolled infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA etc.)
4. Patient/parent/guardian unable to give informed consent or unable to comply with the treatment protocol.
5. Pregnant or lactating women
6. Other uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 9

1. Death from any cause from the day of randomization.
2. Non-response at 28 days
3. Cumulative incidence of relapse is defined as time from CAR T cell infusion until disease relapse in patients with a morphological complete response on day 28
4. Cumulative incidence of initiation of anti-leukemic therapy during the first two years after CAR T cell infusion
5. Type, incidence, severity, seriousness and relationship of CRS, ICANS, IEC-HS, cytopenia day 28 – day 180 (grade 3-4), and infectious adverse events (grade ≥3) during the first 180 days after CAR T cell infusion
6. Duration of B-cell aplasia and CAR T cell numbers from the day of CAR T cell infusion until 1 year
7. Duration of B-cell aplasia in the bone marrow from the day of CAR T cell infusion until 6 months after CAR T cell infusion
8. Definition of accuracy of fludarabine therapeutic drug monitoring (percentage of patients within the target of 18 mg*h/L, range 17.5-18.5 mg*h/L)
9. Patient-reported outcome measures

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

Dr. Friso Calkoen

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

TDC Secretary

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications