Fecal Microbiota Transplantation for Steroid-Refractory Acute GI GVHD

Fecal Microbiota Transplantation for the Treatment of Steroid Refractory Acute Gastrointestinal Graft-Versus-Host Disease in Patients After Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Biological: Fecal microbiota transplantation (FMT)

Detailed Description

This is a prospective, single-arm, open-label, phase II clinical trial evaluating the safety and efficacy of fecal microbiota transplantation (FMT) in adult patients with steroid-refractory acute gastrointestinal graft-versus-host disease (acute GI-GvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible patients will receive 250 cc microbiota fluid prepared from healthy screened donors, delivered into the terminal ileum or cecum via ileocolonoscopy, or into the terminal duodenum via panendoscopy. The study aims to assess event-free survival, overall and complete response rates, survival outcomes, changes in steroid exposure, adverse events, and microbiological/immunological biomarkers. A total of 35 participants will be enrolled over a planned 2-year study period.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hsiao-Wen Kao, M.D.; Phone Number: 2524 +886-3-3281200; Email: hsiaowen@cgmh.org.tw
• Study Contact Backup: Name: Tung-Lian Lin, M.D.; Phone Number: 2534 +886-3-3281200; Email: ldl2605@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333423
    • Recruiting
    • Chang Gung Memorial Hospital at Linkou
    • Contact: Hsiao-Wen Kao, M.D.; Phone Number: 2524 +886-3-3281200; Email: hsiaowen@cgmh.org.tw

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Stage II to IV steroid refractory acute GI-GvHD in allo-HSCT recipients

   1. 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
   2. Resistant to a first-line therapy with corticosteroids (CS)
   1. Lack of improvement after 5 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose,
   2. Progression after 3 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose.
2. Age ≥ 18 years old.
3. Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen.
4. 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.
5. 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)
6. 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.

Exclusion Criteria:

1. Absolute neutrophil count < 500 cells/uL.
2. Absolute platelet count < 30000 /uL which is not correctable by transfusion
3. 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.
4. Uncontrolled and active infection from bacteria, virus, or fungus as determined by the investigators.

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: single arm; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	at least one stage improvement in acute GI-GvHD	on day-56 after first FMT
Complete response rate	improvement of acute GI-GvHD to stage 0	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	Relapse defined as at least one stage acute gastrointestinal GvHD progression.	at least two-year follow-up after first FMT
Overall survival		from the time of first FMT to the time of death.
Non-relapse mortality	death without prior acute gastrointestinal GvHD relapse	at least two-year follow-up after first FMT
Incidence of adverse events	adverse events include but not limited to infection, cytopenia, viral reactivation, gastrointestinal bleeding, bowel rupture	at least two-year follow-up after first FMT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of changes in severity of endoscopic abnormalities and/or histologic evidence of acute GI GVHD relative to baseline assessment.	Gastrointestinal mucosa improvement observed by ileocolonoscopy or panendoscopy findings, or histopathology findings from gastrointestinal tract biopsy	on second or third FMT
Changes in GvHD related biomarkers		on day-28 after first FMT

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: National Taiwan University Hospital
• Investigators: Principal Investigator: Hsiao-Wen KAO, M.D., Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: fecal microbiota transplantation; steroid-refractory; Acute Gastrointestinal Graft-versus-Host Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: 202401777A0; LK20250520001 (Other Grant/Funding Number: Chang Gung Medical Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study team plans to share de-identified individual participant data (IPD), including clinical outcomes, laboratory results, and response assessments related to fecal microbiota transplantation for acute GI-GvHD. IPD will be made available after publication of the primary results and following completion of all planned analyses. Data will be shared in a de-identified, password-protected format and will be accessible upon reasonable request to the principal investigator through a formal data-sharing agreement specifying intended use, data protection measures, and prohibition of re-identification. Supporting documents (such as the protocol and statistical analysis plan) may also be available upon request. No public repository upload is currently planned.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No