Fecal Microbiota Transplantation for Steroid-Refractory Acute GI GVHD

NCT07364617 | Not Yet Recruiting Phase 2

• 2 other identifiers: 202401777A0LK20250520001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for various hematologic diseases. However, one of the major challenges of allo-HSCT is the occurrence of graft-versus-host disease (GvHD), particularly acute gastrointestinal GvHD (GI-GvHD). GvHD occurs when donor T cells recognize the recipient's tissue as foreign and mount an immune attack against it. Acute GI-GvHD is a common complication following allo-HSCT and a significant cause of mortality. If the initial steroid treatment for acute GvHD fails, mortality rates can reach as high as 81%. Recent studies have shown a strong association between reduced gut microbiota diversity and high mortality in patients with acute GI-GvHD, highlighting the critical role of the gut microbiome in regulating immune responses and maintaining intestinal homeostasis. Consequently, fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy aimed at restoring a healthy gut microbiome and improving clinical outcomes in patients with acute GI-GvHD. This study aims to evaluate the efficacy and safety of FMT in patients with steroid-refractory or steroid-resistant acute GI-GvHD. The findings of this research will contribute to establishing FMT as a potential and effective treatment option for managing severe acute GI-GvHD, thereby improving patient outcomes and reducing transplant-related mortality.

Conditions

Graft vs Host Disease

Keywords

Acute Gastrointestinal Graft-versus-Host Disease; fecal microbiota transplantation; steroid-refractory

Outcome Measures

Primary Outcomes (3)

• event-free survival

  From first fecal microbiota transplantation to the first event or up to 6 months

• overall response rate

  at least one stage improvement in acute GI-GvHD

  on day-28 after first FMT

• complete response rate

  improvement of acute GI-GvHD to stage 0

  on day-28 after first FMT

Secondary Outcomes (7)

• Overall response rate

  on day-56 after first FMT

• Complete response rate

  on day 56 after first FMT

• Time to response

  from the time of first FMT to the time of at least one stage improvement in acute GI-GvHD

• Relapse rate

  at least two-year follow-up after first FMT

• Overall survival

  from the time of first FMT to the time of death.

Other Outcomes (2)

• Incidence of changes in severity of endoscopic abnormalities and/or histologic evidence of acute GI GVHD relative to baseline assessment.

  on second or third FMT

• Changes in GvHD related biomarkers

  on day-28 after first FMT

Study Arms (1)

single arm

EXPERIMENTAL

Participants receive 250 mL microbiota fluid delivered to the terminal ileum/cecum via ileocolonoscopy or to the duodenum via panendoscopy, with a second FMT given 7-21 days later and an optional third dose based on response.

Biological: Fecal microbiota transplantation (FMT)

Interventions

Fecal microbiota transplantation (FMT) BIOLOGICAL

About 250 mL microbiota fluid, containing approximately 60 cm³ of stool materials; 6x10¹³ bacteria, will be delivered to the terminal ileum/cecum via ileocolonoscopy or to the duodenum via panendoscopy, with a second FMT given 7-21 days later and an optional third dose based on response.

single arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage II to IV steroid refractory acute GI-GvHD in allo-HSCT recipients
• Stage II to IV acute GI-GVHD subjects, having \>1000 mL stool per day, diarrhea \> 5 times/day, or abdominal cramping, bleeding or ileus, AND
• Resistant to a first-line therapy with corticosteroids (CS)
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• Lack of improvement after 5 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose,
• Progression after 3 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose.
• Age ≥ 18 years old.
• Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen.
• Allow vancomycin-resistant enterococcus (VRE) colonization and asymptomatic cytomegalovirus (CMV) viremia, which is defined as a detectable CMV viral load in plasma but without tissue-invasive disease.
• Patients able to have a minimum of 12 hours discontinuation of systemic antibiotics in order to perform the allogeneic FMT (antiviral and antifungal agents are allowed)
• Signature of informed and written consent by the subject or by the subject's legally acceptable representative for patients under guardianship or trusteeship. Subject must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.

You may not qualify if:

• Absolute neutrophil count \< 500 cells/uL.
• Absolute platelet count \< 30000 /uL which is not correctable by transfusion
• Hemodynamically unstable status with the following conditions: systolic blood pressure \< 90 mm Hg, pulse oximeter oxygen saturation (SpO2) \< 90%, PaO2 \< 60 mm Hg, or respiratory rate \> 22/minute.
• Uncontrolled and active infection from bacteria, virus, or fungus as determined by the investigators.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• National Taiwan University Hospital: collaborator

Study Sites (2)

Chang Gung Memorial Hospital at Linkou

Taoyuan District, 333423, Taiwan

Location

Chang Gung Memorial Hospital at Linkou

Taoyuan District, 333423, Taiwan

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Hsiao-Wen KAO, M.D.

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hsiao-Wen Kao, M.D.

CONTACT

+886-3-3281200; hsiaowen@cgmh.org.tw

Tung-Lian Lin, M.D.

CONTACT

+886-3-3281200; ldl2605@cgmh.org.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Division of Hematology-Oncology

Model Details: This prospective, single-arm, open-label phase II study evaluates fecal microbiota transplantation (FMT) as treatment for adults with steroid-refractory stage II-IV acute gastrointestinal graft-versus-host disease (GI-GvHD) after allogeneic hematopoietic stem cell transplantation. Participants receive 250 mL microbiota fluid delivered to the terminal ileum/cecum via ileocolonoscopy or to the duodenum via panendoscopy, with a second FMT given 7-21 days later and an optional third dose based on response. The study assesses event-free survival, overall and complete response rates at Days 28 and 56, steroid reduction, relapse, survival, and safety including infections and procedure-related complications. Serial clinical, microbiologic, and immunologic evaluations are performed to characterize treatment effects and adverse events. Total planned enrollment is 35 patients.

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: January 23, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: De-identified individual participant data (IPD) and supporting documents (such as the study protocol and statistical analysis plan) will be available starting 12 months after publication of the primary study results. Data will remain available for 5 years after that date. Access will be provided upon reasonable request through a data-sharing agreement with the principal investigator.
• Access Criteria: De-identified individual participant data and supporting documents (including the protocol and statistical analysis plan) will be accessible to qualified researchers, academic investigators, research organizations, and regulatory authorities that submit a methodologically sound proposal aligned with the study's scientific objectives. Approved requestors will gain access after signing a data-sharing agreement specifying data-use restrictions, data-security requirements, and a prohibition on re-identification. Data will be shared in a secure, password-protected electronic format provided directly by the study team.

Locations

TW (2)