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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Graft Versus Host Disease in Intestine
• Intervention / Treatment: Biological: Fecal Microbial Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pietro Merli, MD; Phone Number: +390668592623; Email: pietro.merli@opbg.net

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Riccardo Masetti, MD, PhD; Phone Number: +39 051 2144016; Email: riccardo.masetti5@unibo.it
  • Padova, Italy, 35128
    • UOC Clinica di Oncoematologia Pediatrica, Azienda Ospedale-Università Padova
    • Contact: Maria Gabelli, MD; Phone Number: +39 049 8213579; Email: maria.gabelli@aopd.veneto.it
  • Roma, Italy, 00165
    • Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital
    • Contact: Pietro Merli, MD; Phone Number: +390668592623; Email: pietro.merli@opbg.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; FMT

Biological: Fecal Microbial Transplantation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (AE and treatment-related AE, according to CTCAE v5.0)	Number of Participants With Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v5.0	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Overall Response Rate (ORR)	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).	28 days
Microbiota modification	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).	56 days
Cumulative incidence of infections	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.	28 days
Efficacy on other GVHD target organs	Response in skin and liver GVHD involvement according to MAGIC criteria.	56 days
Immune reconstitution	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.	90 days

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute
• Collaborators: IRCCS Azienda Ospedaliero-Universitaria di Bologna; University Hospital, Padua, Italy

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: 3444_OPBG_2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No