FMT for Pediatric SR-aGVHD
Fecal Microbiota Transplantation for the Treatment of Steroid-refractory Graft-versus-host Disease.
This is a pilot, prospective, non-profit, multicenter, uncontrolled, open-label study to evaluate the safety and feasibility of FMT in patients aged between 3 months and 25 years suffering from acute intestinal GVHD resistant to conventional steroid therapy.
Eligible patients will receive 1-3 FMT via naso-jejunal tube or endoscopy.
연구 개요
연구 유형
등록 (추정된)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Pietro Merli, MD
- 전화번호: +390668592623
- 이메일: pietro.merli@opbg.net
연구 장소
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Bologna, 이탈리아, 40138
- Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
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연락하다:
- Riccardo Masetti, MD, PhD
- 전화번호: +39 051 2144016
- 이메일: riccardo.masetti5@unibo.it
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Padova, 이탈리아, 35128
- UOC Clinica di Oncoematologia Pediatrica, Azienda Ospedale-Università Padova
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연락하다:
- Maria Gabelli, MD
- 전화번호: +39 049 8213579
- 이메일: maria.gabelli@aopd.veneto.it
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Roma, 이탈리아, 00165
- Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital
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연락하다:
- Pietro Merli, MD
- 전화번호: +390668592623
- 이메일: pietro.merli@opbg.net
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Diagnosis of hematological disease, malignant or non-malignant;
- Patients undergoing allogeneic stem cell transplantation from a familial or unrelated donor;
- Presence of acute GVHD with intestinal involvement (grade II-IV), steroid-resistant (i.e., with progression after 3 days of high-dose steroid therapy (methylprednisolone > 2 mg/kg), no response after 7 days, progression during steroid tapering, or failure to achieve remission on day 28 from the start of steroid therapy), for those who have no indication for other second- or third-line therapies;
- Signed informed consent.
Exclusion Criteria:
- Presence of concurrent bacterial infections requiring systemic antibiotic therapy;
- Positivity for anti-HIV or anti-HCV antibodies, or for HbsAg with HBV-DNA positive by PCR;
- Presence of severe mucositis;
- History of chronic inflammatory bowel disease.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Treatment
FMT
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The administration of the fecal preparation (from a related donor or a third party donor) will be carried out via esophagogastroduodenoscopy, with the release of the fecal preparation into the duodenum; or via a nasoduodenal tube, with the release of the fecal preparation into the duodenum at a 'dose' of 7-12 ml/kg, up to a maximum of 250 ml/administration; or via colonoscopy. In the latter case, mucosal biopsies will not be performed to reduce the risk of bacterial translocation. In some subjects, the possibility of administering the emulsion via ENEMA will be evaluated. Cases will be selected based on specific clinical indications. In the case of a partial response, after evaluating the risk/benefit ratio, a second infusion can be performed after 3 days. The procedure can be repeated a third time later (7 days) in case of a new flare of intestinal GVHD after initial improvement. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Safety (AE and treatment-related AE, according to CTCAE v5.0)
기간: 28 days
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Number of Participants With Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v5.0
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28 days
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Efficacy: Overall Response Rate (ORR)
기간: 28 days
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Number of participants with Complete Response (CR, defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD) or Partial Response (PR, defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD) at day +28 according to MAGIC criteria (ORR=CR+PR).
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28 days
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Microbiota modification
기간: 56 days
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Comparison of alpha-diversity (according to Chao And Simpson indexes) and of beta-diversity (according to Bray-Curtis and UniFrac dissimilarity indexes) of patient samples taken before and after FMT (16s sequencing).
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56 days
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Cumulative incidence of infections
기간: 28 days
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Cumulative incidence of clinically-relevant infections (i.e., ≥ grade 3 according to CTCAE v 5.0) after FMT; relapse or start of a new immunosuppressive treatment will be considered competing events.
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28 days
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Efficacy on other GVHD target organs
기간: 56 days
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Response in skin and liver GVHD involvement according to MAGIC criteria.
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56 days
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Immune reconstitution
기간: 90 days
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Number of participants with CD3+ counts > 500/mcl at day +90 after treatment.
Number of participants with CD4+ counts > 50/mcl at day +90 after treatment.
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90 days
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공동 작업자 및 조사자
간행물 및 유용한 링크
일반 간행물
- van Lier YF, Davids M, Haverkate NJE, de Groot PF, Donker ML, Meijer E, Heubel-Moenen FCJI, Nur E, Zeerleder SS, Nieuwdorp M, Blom B, Hazenberg MD. Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med. 2020 Aug 12;12(556):eaaz8926. doi: 10.1126/scitranslmed.aaz8926.
- Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, Sugiyama D, Nishikawa H, Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, Koizumi K, Honda K, Ohashi K. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016 Oct 20;128(16):2083-2088. doi: 10.1182/blood-2016-05-717652. Epub 2016 Jul 26.
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
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