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

13. května 2026 aktualizováno: Swiss Cancer Institute

Bendamustine Versus Fludarabine/Cyclophosphamide for Lymphodepletion in CAR-T Therapy: a Randomized Trial

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).

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

Chimeric antigen receptor (CAR) T-cell immunotherapy (CAR-T) has emerged as an effective treatment for relapsed/refractory aggressive B-cell lymphomas. Three products that demonstrate clinical activities in relapse/refractory large B-Cell Lymphoma (LBCL), axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel are currently available. To ensure an optimal CAR-T cell expansion and proliferation inside the host once infused, lymphodepleting therapy is administered before CAR-T immunotherapy as it exerts its activities by generating the optimal cytokine and metabolites milieu to ensure engraftment and proliferation of CAR-T cells once infused, by removing anergic circulating lymphocytes responsible of the "cytokine sink effect", and by debulking immunosuppressive tumor masses by the time of CAR-T cell infusion. Nowadays, commercially approved CAR-T products use a combination of fludarabine (Flu) and cyclophosphamide (Cy), at different dosages, as the standard lymphodepletion regimen. After CAR-T cell infusion participants might experience several toxicities including hematological toxicities and resulting infective events, as a direct consequence of lymphodepleting chemotherapy infusion.

Furthermore, the participants can experience CAR-T specific toxicities such as cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS), which are the consequence of the CAR-T cell to tumor engagement activity. In fact, these toxicities are responsible for more than 60% of non-relapse mortalities after CAR-T cells and their treatment increase the hospitalization stay and overall costs of CAR-T cell immunotherapy.

Therefore, there is a great need to improve the current CAR-T cell immunotherapy treatment to reduce the risk of toxicity. A growing number of retrospective studies demonstrated that bendamustine lymphodepletion is an alternative lymphodepletion regimen. In all these studies, bendamustine lymphodepletion showed comparable response rate but drastically reduced toxicities, in terms of CRS, neurotoxicity, hematological toxicity and, in particular, infections. As a result, its use is steadily increasing across Swiss centers. There are no published and other randomized trials, currently ongoing, investigating this particular question. For these reasons, bendamustine should be tested against the current SoC lymphodepleting chemotherapy.

This trial aims to prospectively compare the safety and efficacy of bendamustine versus standard Flu/Cy lymphodepletion before CART cell therapy in participants with relapsed/refractory large B-cell lymphoma (LBCL).

Typ studie

Intervenční

Zápis (Odhadovaný)

92

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní místa

  • Švýcarsko
      • Aarau, Švýcarsko, 5001
        • Kantonsspital Aarau
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Martina Dickenmann, MD
      • Basel, Švýcarsko, 4056
        • Universitätsspital Basel
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Andreas Holbro, MD
      • Bellinzona, Švýcarsko, 6500
        • Ente Ospedaliero Cantonale (EOC)-Istituto Oncologico della Svizzera Italiana (IOSI)
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Georg Stüssi, Prof
      • Bern, Švýcarsko, 3010
        • Inselspital Bern - Universitätsklinik für Medizinische Onkologie
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Marc Wehrli, MD
      • Chur, Švýcarsko, 7000
        • Kantonsspital Graubünden
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Ulrich Mey, MD
      • Geneva, Švýcarsko, 1211
        • Les hôpitaux universitaires de Genève
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Federico Simonetta, MD
      • Lucerne, Švýcarsko, 6004
        • Luzerner Kantonsspital
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Ramona Merki, MD
      • Sankt Gallen, Švýcarsko, 9007
        • HOCH Health Ostschweiz - Kantonsspital St. Gallen
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Martin Fehr, MD
      • Zurich, Švýcarsko, 8032
        • Klinik für Hämatologie und Onkologie Hirslanden Zürich
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Christoph Renner, Prof

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Arm A: Experimental Arm
Bendamustine
Lék: bendamustine hydrochloride
  • 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)
Aktivní komparátor: Arm B: Control Arm
Fludarabine/Cyclophosphamide
Lék: Cyclophosphamide
  • 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.
Lék: Fludarabine
  • 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.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
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)
Časové okno: From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion

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

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

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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Best lymphoma response at 3 months post-CAR-T infusion
Časové okno: From the CAR-T infusion until week 15 (inclusive) post-CAR-T infusion
Best lymphoma response at 3 months is defined as the best response assessment in the following descending order: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable (NE), measured as indicated on local guidelines (e.g., Lugano 2014 classification) based on PET/CT imaging. Any assessment up to week 15 (inclusive) will be considered for determining the best response.
From the CAR-T infusion until week 15 (inclusive) post-CAR-T infusion
Progression-free survival (PFS)
Časové okno: from CAR-T infusion to lymphoma progression or death, up to 3.25 years after CAR-T infusion of the first patient]
PFS is defined as time from CAR-T infusion to lymphoma progression or death from any cause. Participants not experiencing an event, including participants receiving a subsequent anti-lymphoma therapy without documented disease progression or relapse, will be censored at the last time they were known to be without progression (i.e. last date of tumor assessment without progression) and before the start of a new anti-lymphoma treatment, if any.
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)
Časové okno: From CAR-T infusion to death, up to 3.25 years after CAR-T infusion of the first patient
Time from CAR-T infusion to death from any cause. Participants not experiencing an event will be censored at the last date they were known to be alive.
From CAR-T infusion to death, up to 3.25 years after CAR-T infusion of the first patient

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Swiss Cancer Institute

Vyšetřovatelé

  • Studijní židle: Benjamin Kasenda, PD Dr. med. Dr. phil., University Hospital Basel (USB)
  • Ředitel studie: Guido Ghilardi, Ente Ospedaliero Cantonale (EOC)

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. září 2026

Primární dokončení (Odhadovaný)

1. března 2029

Dokončení studie (Odhadovaný)

1. března 2030

Termíny zápisu do studia

První předloženo

4. května 2026

První předloženo, které splnilo kritéria kontroly kvality

13. května 2026

První zveřejněno (Aktuální)

18. května 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

18. května 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

13. května 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • SCI-003_FC-BALANCE
  • 2026-525792-36-00 (Ctis)
  • U1111-1335-8513 (Jiný identifikátor: ICTRP)

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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