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

Acute Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06026371
• Other study ID #: RG1123691
• Secondary ID: NCI-2023-05599RG
• Status: Recruiting
• Phase: Phase 2
• Start date: December 12, 2023
• Est. completion date: September 30, 2026

Study information

• Verified date: March 2024
• Source: Fred Hutchinson Cancer Center
• Contact: Armin Rashidi
• Phone: 206-667-2506
• Email: arashidi[@]fredhutch.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Fecal Microbiota Transplantation Capsule
Given PO
• Placebo
Given PO

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade III-IV acute graft versus host disease (GVHD)	Based on IBMTR criteria and measured as a probability	Up to 6 months post hematopoietic cell transplantation (HCT)
Secondary	Grade II-IV acute GVHD	Based on IBMTR criteria and measured as a probability	Up to 180 days post HCT
Secondary	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
Secondary	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
Secondary	Chronic GVHD	Diagnosis based on the NIH Consensus Criteria (PMID: 25529383)	At 12 months post-HCT