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

Phase 2

Recruiting

• Conditions: Acute Graft Versus Host Disease; Hematopoietic and Lymphatic System Neoplasm
• Interventions: Drug: Fecal Microbiota Transplantation Capsule; Drug: Placebo

• Registration Number: NCT06026371
• Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-08-30
• Study First Submitted QC: 2023-08-30
• Study First Posted: 2023-09-07
• Study Start: 2023-12-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-21
• Primary Completion: 2026-09-30
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 138

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)

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (fecal microbiota transplant)	Fecal Microbiota Transplantation Capsule	Patients receive fecal microbiota capsules PO QD for 7 days
Group II (Placebo)	Placebo	Patients receive placebo PO QD for 7 days

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States