Fecal Microbiota Transplantation for the Prevention of Acute Graft Versus Host Disease in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation

Fecal Microbiota Transplantation to Prevent Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

This randomized placebo-controlled double-blind phase II trial tests whether fecal microorganism (microbiota) transplantation prevents severe acute graft versus host disease in adults undergoing allogeneic hematopoietic cell transplantation (HCT). Fecal microbiota transplantation involves receiving processed fecal material orally after allogeneic HCT in order to establish a healthy gut microbiota. Gut microbiota undergoes major alterations during allogeneic HCT because of antibiotic exposures, nutritional changes, and chemotherapy administration. Establishing a healthy gut microbiota via fecal transplantation may help prevent acute graft versus host disease in patients undergoing allogeneic HCT.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Graft Versus Host Disease; Hematopoietic and Lymphatic System Neoplasm
• Intervention / Treatment: Drug: Fecal Microbiota Transplantation Capsule; Drug: Placebo

Detailed Description

OUTLINE: The first 12 patients are assigned to group I, remaining patients are randomized to 1 of 2 groups.

GROUP I: Patients receive fecal microbiota capsules orally (PO) once daily (QD) for 7 days starting at the time of neutrophil engraftment and discontinuation of anti-bacterial antibiotics.

GROUP II: Patients receive placebo PO QD for 7 days starting at the time of neutrophil engraftment and discontinuation of anti-bacterial antibiotics.

After completion of study intervention, patients are followed up monthly until 12 months post-allogeneic HCT.

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age >= 18
• Signed informed consent
• Able to take oral medications
• Planned T-replete allogeneic hematopoietic cell transplantation for any indication. History of prior transplantation is allowed

• Planned GVHD prophylaxis using one of the following regimens:

  • Calcineurin inhibitor (tacrolimus or cyclosporine) plus methotrexate
  • Calcineurin inhibitor (tacrolimus or cyclosporine) plus mycophenolate mofetil (MMF)
  • Sirolimus plus cyclosporine plus MMF
  • Post-transplant cyclophosphamide plus calcineurin inhibitor (with or without MMF or sirolimus)

• One of the following HCT donor types:

  • Human leukocyte antigen (HLA)-matched sibling donor
  • 9/10 or 10/10 HLA-matched unrelated donor
  • HLA- haploidentical donor
  • Cord blood
• Willing to use at least 1 accepted method of contraception until day 180 after transplant and agree to not donate eggs/sperm for 180 days after
• Not pregnant or breast feeding
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: Absolute neutrophil count (ANC) recovery to > 0.5 x 10^9/L from nadir, without ongoing growth factor support
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: Discontinuation of all antibacterial antibiotics (except those used for Pneumocystis jiroveci prophylaxis) for 2 days
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: Resolution of all acute toxicities (other than anemia and thrombocytopenia) to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or lower
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: Ability to swallow capsules
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: No grade II-IV acute GVHD
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: No moderate to severe chronic GVHD
• ELIGIBILITY CRITERIA FOR RANDOMIZATION: No concurrent antibiotics to treat infections. Prophylactic antiviral and antifungal antibiotics used to prevent infections are allowed

Exclusion Criteria:

• Severe food allergy in the form of anaphylaxis or attributable symptoms requiring hospitalization
• History of chronic aspiration or conditions predisposing to aspiration (e.g. neuromuscular disorders)
• Receiving or planned to receive other experimental agents (including ex vivo T-cell depletion) to prevent GVHD. The use of other experimental agents is prohibited unless approved by the principal investigator (PI) of the other trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (fecal microbiota transplant); Patients receive fecal microbiota capsules PO QD for 7 days	Drug: Fecal Microbiota Transplantation Capsule; Given PO; Other Names: Fecal Microbiota Preparation Delivery Capsule; FMPCapDE; FMT Capsule DE; FMT Capsule Delivery; FMT DE Capsule
Placebo Comparator: Group II (Placebo); Patients receive placebo PO QD for 7 days	Drug: Placebo; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade III-IV acute graft versus host disease (GVHD)	Based on International Blood and Marrow Transplantation Research (IBMTR) criteria and measured as a probability	Up to 6 months post hematopoietic cell transplantation (HCT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade II-IV acute GVHD	Based on IBMTR criteria and measured as a probability	Up to 180 days post HCT
Non-relapse mortality	Death not due to relapse/progression of the underlying hematologic disorder and measured as a probability	Up to 180 days post HCT
Clostridium difficile diarrhea	Based on a positive stool assay in the consistent clinical setting (e.g. diarrhea) and measured as a probability	Up to 180 days post HCT
Chronic GVHD	Diagnosis based on the National Institutes of Health Consensus Criteria (PMID: 25529383)	At 12 months post-HCT

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Armin Rashidi, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

General Publications

• Reddi S, Senyshyn L, Ebadi M, Podlesny D, Minot SS, Gooley T, Kabage AJ, Hill GR, Lee SJ, Khoruts A, Rashidi A. Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect. Nat Commun. 2025 Jan 25;16(1):1034. doi: 10.1038/s41467-025-56375-y.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: August 30, 2023
• First Submitted That Met QC Criteria: August 30, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Therapeutics; Biological Therapy; Pregnancy; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Parturition; Fecal Microbiota Transplantation
• Other Study ID Numbers: RG1123691 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2023-05599 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); FHIRB0020155 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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