Bendamustine Versus Fludarabine/Cyclophosphamide for Lymphodepletion in Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T): a Randomized Trial.

NCT07593482 | Not Yet Recruiting Phase 2 DMC

• 3 other identifiers: SCI-003_FC-BALANCE2026-525792-36-00U1111-1335-8513
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 9

Brief Summary

Bendamustine and the combination of fludarabine/cyclophosphamide are fully authorized chemotherapy agents in Switzerland for lymphoma treatment and currently used in routine clinical practice as lymphodepletion strategy before CAR-T immunotherapy, as supported by retrospective studies and clinical experience across multiple centers. None of the drugs described in this protocol are being used at unapproved doses, or in an investigational formulation. Both lymphodepletion regimens have a known safety profile and the risks and burdens imposed on participants do not exceed those encountered in routine CAR-T therapy management, as all procedures (including monitoring, supportive care, and follow-up assessments) align with standard clinical practice. Based on these assumptions, this protocol is designed to investigate the use of bendamustine as an alternative lymphodepletion therapy (which is a part of CAR-T immunotherapy protocol).

Conditions

B-cell Lymphoma

Keywords

Large B-cell lymphoma; LBCL; B-cell malignancy; Chimeric antigen receptor (CAR) T-cell therapy; Bendamustine; Fludarabine/Cyclophosphamide; lymphodepletion in CAR-T therapy

Outcome Measures

Primary Outcomes (3)

• Incidence of the following side effect occurring within 4 weeks (28 days) from the CAR-T infusion: Occurrence of grade ≥3 cytokine release syndrome (CRS)

  Primary Outcome measure consists of 3 side effects: Incidence of at least one of the following side effects occurring within 4 weeks (28 days) from the CAR-T infusion: • Occurrence of grade ≥3 cytokine release syndrome (CRS) • Febrile neutropenia • Grade ≥3 Immune effector Cell-Associated Neurotoxicit. All infections, including those that result in febrile neutropenia, and the CRS and ICANS will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Febrile neutropenia is defined as absolute neutrophil count \<1000/mm³ with fever ≥38.3°C (single measurement) or ≥38.0°C sustained for \>1 hour. Participants who remain free of any of the above listed symptoms at least 28 days from the CAR-T cell infusion AND did not stop the trial treatment will be counted as a success for this endpoint, otherwise they will be counted as a failure for the primary endpoint.

  From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion

• Incidence of the following side effect occurring within 4 weeks (28 days) from the CAR-T infusion: Febrile neutropenia

  Primary Outcome measure consists of 3 side effects: Incidence of at least one of the following side effects occurring within 4 weeks (28 days) from the CAR-T infusion: • Occurrence of grade ≥3 cytokine release syndrome (CRS) • Febrile neutropenia • Grade ≥3 Immune effector Cell-Associated Neurotoxicit. All infections, including those that result in febrile neutropenia, and the CRS and ICANS will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Febrile neutropenia is defined as absolute neutrophil count \<1000/mm³ with fever ≥38.3°C (single measurement) or ≥38.0°C sustained for \>1 hour. Participants who remain free of any of the above listed symptoms at least 28 days from the CAR-T cell infusion AND did not stop the trial treatment will be counted as a success for this endpoint, otherwise they will be counted as a failure for the primary endpoint.

  From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion

• Incidence of the following side effect occurring within 4 weeks (28 days) from the CAR-T infusion: Grade ≥3 Immune effector Cell-Associated Neurotoxicit

  All infections, including those that result in febrile neutropenia, and the CRS and ICANS will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Febrile neutropenia is defined as absolute neutrophil count \<1000/mm³ with fever ≥38.3°C (single measurement) or ≥38.0°C sustained for \>1 hour. Participants who remain free of any of the above listed symptoms at least 28 days from the CAR-T cell infusion AND did not stop the trial treatment will be counted as a success for this endpoint, otherwise they will be counted as a failure for the primary endpoint.

  From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion

Secondary Outcomes (3)

• Best lymphoma response at 3 months post-CAR-T infusion

  From the CAR-T infusion until week 15 (inclusive) post-CAR-T infusion

• Progression-free survival (PFS)

  from CAR-T infusion to lymphoma progression or death, up to 3.25 years after CAR-T infusion of the first patient]

• Overall survival (OS)

  From CAR-T infusion to death, up to 3.25 years after CAR-T infusion of the first patient

Study Arms (2)

Arm A: Experimental Arm

EXPERIMENTAL

Bendamustine

Drug: bendamustine hydrochloride

Arm B: Control Arm

ACTIVE COMPARATOR

Fludarabine/Cyclophosphamide

Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

bendamustine hydrochloride DRUG

* Dose: 90 mg/m² body surface area * Route: Intravenous infusion * Administration: Infused over 30-60 minutes in 500 mL normal saline or 5% dextrose * Pre-medication: Standard institutional protocols for bendamustine administration (typically antiemetics)

Arm A: Experimental Arm

Cyclophosphamide DRUG

* Administration: Intravenous infusion per institutional protocols and product guidelines. * Dose: according to the specification described in the prescription information sheet of the CAR-T product used.

Arm B: Control Arm

Fludarabine DRUG

* Administration: Intravenous infusion per institutional protocols and product guidelines. * Dose: according to the specification described in the prescription information sheet of the CAR-T product used.

Arm B: Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of large B-cell lymphoma (LBCL) with at least one line of previous treatment and indication for commercial CAR-T cell therapy as determined by the treating physician. This includes: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS) and all specific DLBCL subtypes, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma, and other transformed indolent B-cell lymphomas (including transformed marginal zone lymphoma and Richter's transformation). Patients with primary or secondary central nervous system (CNS) involvement are eligible.
• Planned treatment with commercially available CAR-T cell product
• Age ≥18 years
• Ability to provide written informed consent

You may not qualify if:

• Administration of any other experimental drug within 5 half-lives or ≤ 4 weeks prior to lymphodepletion therapy starts.
• Bendamustine 3 months before leukapheresis. After leukapheresis, bendamustine use is allowed as bridging therapy according to physician decision.
• Previous administration of anti-CD19 CAR-T products within the last 12 months from lymphodepletion therapy start.
• Known history of hypersensitivity to the active substance or any of the excipients found in the composition of bendamustine, fludarabine, or cyclophosphamide.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (9)

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Universitätsspital Basel

Basel, 4056, Switzerland

Location

Ente Ospedaliero Cantonale (EOC)-Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

Location

Inselspital Bern - Universitätsklinik für Medizinische Onkologie

Bern, 3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Les hôpitaux universitaires de Genève

Geneva, 1211, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6004, Switzerland

Location

HOCH Health Ostschweiz - Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Klinik für Hämatologie und Onkologie Hirslanden Zürich

Zurich, 8032, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Bendamustine Hydrochloride; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Officials

• Benjamin Kasenda, PD Dr. med. Dr. phil.

  University Hospital Basel (USB)

  STUDY CHAIR

• Guido Ghilardi

  Ente Ospedaliero Cantonale (EOC)

  STUDY DIRECTOR

Central Study Contacts

Ana Bello Gamboa

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentre, open-label, randomized (1:1 allocation), parallel-group superiority trial comparing two lymphodepletion regimens in participants with large B-cell lymphoma undergoing CAR-T cell therapy. After treatment, all patients will be followed up until last participant completes 12 months of follow-up.

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: May 18, 2026

Record last verified: 2026-05

Locations

CH (9)