Clinical trial NCT06026371: Fecal Microbiota Transplantation for the Prevention of Acute Graft Versus Host Disease in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation
Official title: Fecal Microbiota Transplantation to Prevent Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Graft Versus Host Disease
Hematopoietic and Lymphatic System Neoplasm
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
First posted: 2023-09-07
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The first 12 patients are assigned to the treatment group, remaining patients are randomized to treatment or placebo group.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Grade III-IV acute graft versus host disease (GVHD)
timeFrame: Up to 6 months post hematopoietic cell transplantation (HCT)
Secondary outcomes:
measure: Grade II-IV acute GVHD
timeFrame: Up to 180 days post HCT
measure: Non-relapse mortality
timeFrame: Up to 180 days post HCT
measure: Clostridium difficile diarrhea
timeFrame: Up to 180 days post HCT
measure: Chronic GVHD
timeFrame: At 12 months post-HCT
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Armin Rashidi
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.