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.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Pietro Merli, MD
- 電話番号：+390668592623
- メール：pietro.merli@opbg.net
研究場所
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Bologna、イタリア、40138
- Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
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コンタクト：
- Riccardo Masetti, MD, PhD
- 電話番号：+39 051 2144016
- メール：riccardo.masetti5@unibo.it
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Padova、イタリア、35128
- UOC Clinica di Oncoematologia Pediatrica, Azienda Ospedale-Università Padova
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コンタクト：
- Maria Gabelli, MD
- 電話番号：+39 049 8213579
- メール：maria.gabelli@aopd.veneto.it
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Roma、イタリア、00165
- Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital
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コンタクト：
- Pietro Merli, MD
- 電話番号：+390668592623
- メール：pietro.merli@opbg.net
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-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Treatment
FMT
|
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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Safety (AE and treatment-related AE, according to CTCAE v5.0)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Efficacy: Overall Response Rate (ORR)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。