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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Graft Versus Host Disease, Hematopoietic and Lymphoid System Neoplasm

Intervention / Treatment
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* Drug: Fecal Microbiota Transplantation Capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The first 12 patients are assigned to the treatment group, remaining patients are randomized to treatment or placebo group.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (fecal microbiota transplant)<br>Patients receive fecal microbiota capsules PO QD for 7 days | Drug: Fecal Microbiota Transplantation Capsule<br>* Given PO<br>* Other names: FMT DE Capsule;|
| Placebo Comparator: Group II (Placebo)<br>Patients receive placebo PO QD for 7 days | Drug: Placebo<br>* Given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 NIH Consensus Criteria (PMID: 25529383) | At 12 months post-HCT |