Bendamustine Versus Fludarabine/Cyclophosphamide for Lymphodepletion in Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T): a Randomized Trial. (FC-BALANCE)
Bendamustine Versus Fludarabine/Cyclophosphamide for Lymphodepletion in CAR-T Therapy: a Randomized Trial
연구 개요
상태
정황
상세 설명
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).
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Ana Bello Gamboa
- 전화번호: +41 31 389 91 91
- 이메일: trials@swisscancerinstitute.ch
연구 장소
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Aarau, 스위스, 5001
- Kantonsspital Aarau
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연락하다:
- Martina Dickenmann, MD
- 전화번호: +41 79 391 22 75
- 이메일: martina.dickenmann@ksa.ch
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수석 연구원:
- Martina Dickenmann, MD
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Basel, 스위스, 4056
- Universitätsspital Basel
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연락하다:
- Andreas Holbro, MD
- 전화번호: +41 61 265 25 25
- 이메일: Andreas.Holbro@usb.ch
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수석 연구원:
- Andreas Holbro, MD
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Bellinzona, 스위스, 6500
- Ente Ospedaliero Cantonale (EOC)-Istituto Oncologico della Svizzera Italiana (IOSI)
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연락하다:
- Georg Stüssi, Prof
- 전화번호: +41 91 811 87 78
- 이메일: Georg.Stuessi@eoc.ch
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수석 연구원:
- Georg Stüssi, Prof
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Bern, 스위스, 3010
- Inselspital Bern - Universitätsklinik für Medizinische Onkologie
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연락하다:
- Marc Wehrli, MD
- 전화번호: +41 31 632 41 11
- 이메일: marc.wehrli@insel.ch
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수석 연구원:
- Marc Wehrli, MD
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Chur, 스위스, 7000
- Kantonsspital Graubunden
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연락하다:
- Ulrich Mey, PD
- 전화번호: +41 81 256 71 70
- 이메일: ulrich.mey@ksgr.ch
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수석 연구원:
- Ulrich Mey, MD
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Geneva, 스위스, 1211
- Les hôpitaux universitaires de Genève
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연락하다:
- Federico Simonetta, MD
- 전화번호: +41 22 372 38 38
- 이메일: federico.simonetta@unige.ch
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수석 연구원:
- Federico Simonetta, MD
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Lucerne, 스위스, 6004
- Luzerner Kantonsspital
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연락하다:
- Ramona Merki, MD
- 전화번호: +41 41 205 51 47
- 이메일: ramona.merki@luks.ch
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수석 연구원:
- Ramona Merki, MD
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Sankt Gallen, 스위스, 9007
- HOCH Health Ostschweiz - Kantonsspital St. Gallen
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연락하다:
- Martin Fehr, MD
- 전화번호: +41 71 494 62 69
- 이메일: martin.fehr@h-och.ch
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수석 연구원:
- Martin Fehr, MD
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Zurich, 스위스, 8032
- Klinik für Hämatologie und Onkologie Hirslanden Zürich
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연락하다:
- Christoph Renner, Prof
- 전화번호: +41 43 387 37 80
- 이메일: christoph.renner@kho.ch
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수석 연구원:
- Christoph Renner, Prof
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Arm A: Experimental Arm
Bendamustine
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활성 비교기: Arm B: Control Arm
Fludarabine/Cyclophosphamide
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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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)
기간: From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion
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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
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Incidence of the following side effect occurring within 4 weeks (28 days) from the CAR-T infusion: Febrile neutropenia
기간: 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
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Incidence of the following side effect occurring within 4 weeks (28 days) from the CAR-T infusion: Grade ≥3 Immune effector Cell-Associated Neurotoxicit
기간: From the start of lymphodepletion therapy until 4 weeks (day 28) after the CAR-T cell Infusion
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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
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Best lymphoma response at 3 months post-CAR-T infusion
기간: From the CAR-T infusion until week 15 (inclusive) post-CAR-T infusion
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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.
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From the CAR-T infusion until week 15 (inclusive) post-CAR-T infusion
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Progression-free survival (PFS)
기간: from CAR-T infusion to lymphoma progression or death, up to 3.25 years after CAR-T infusion of the first patient]
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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.
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from CAR-T infusion to lymphoma progression or death, up to 3.25 years after CAR-T infusion of the first patient]
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Overall survival (OS)
기간: From CAR-T infusion to death, up to 3.25 years after CAR-T infusion of the first patient
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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.
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From CAR-T infusion to death, up to 3.25 years after CAR-T infusion of the first patient
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공동 작업자 및 조사자
수사관
- 연구 의자: Benjamin Kasenda, PD Dr. med. Dr. phil., University Hospital Basel (USB)
- 연구 책임자: Guido Ghilardi, Ente Ospedaliero cantonale (EOC)
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- SCI-003_FC-BALANCE
- 2026-525792-36-00 (씨티스)
- U1111-1335-8513 (기타 식별자: ICTRP)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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