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

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.

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