This phase I trial studies the side effects of using an investigational procedure (fecal microbiota transplantation \[FMT\]) in treating patients with severe acute gut graft-versus-host-disease. The purpose of a fecal microbiota transplantation is to use feces from a healthy human donor to replace the abnormal gut bacteria in the recipient. One of the side effects of a stem cell transplant is the development of graft-versus-host disease (GvHD) in several organs including gut. GvHD is caused by the donated bone marrow or peripheral blood cells recognizing the recipient's body as foreign and attacking it. Acute gut GvHD is one of the leading causes of death after transplant. Recently, studies have shown that patients with reduced intestinal bacterial diversity in their stool during acute gut GvHD have higher overall mortality rates. The information learned from this study may offer FMT as a promising therapy for the treatment of severe acute gut graft-versus-host-disease.
PRIMARY OBJECTIVES: I. For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration. II. For tolerability evaluation, subject must ingest 50% of one dose of FMT product without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT. SECONDARY OBJECTIVE: I. To collect stool, oral swabs and blood specimens for future studies to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD). II. For clinical efficacy, \> 50% of subjects with at least 1 stage of gut GvHD improvement by 8 weeks after the first dose of FMT. OUTLINE: Patients ingest OpenBiome FMT Capsule Dose Extended (DE) orally for two consecutive days. One dose is equivalent to the ingestion of 30 capsules and thus each day the patient will ingest 15 capsules. If no response is noted after 7 days, patients may receive a second dose of FMT for an additional 2 days. Standard treatment for gut GvHD will continue during this time. After completion of study treatment, patients are followed for up to 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Receive OpenBiome FMT Capsule DE PO
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Incidence of adverse events
For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration. For tolerability evaluation, at least 60% of subjects able to ingest 50% of one dose of FMT without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT. Subjects will be monitored via assessment of gut graft versus host disease (GvHD) staging and adverse events will be performed bi-weekly for the first 4 weeks after the first dose of FMT, weekly during the hospitalization and monthly up to six months after hospital discharge.
Time frame: Up to 6 months
Collection of stool, oral swabs and blood specimens to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD)
Alpha diversity metrics will be compared between time points mixed effect regression models. Multivariate differences will be calculated using permutational multivariate analysis of variance (PERMANOVA). Differential abundance techniques will be used to compare taxa over time using DESeq2 package. DESeq2 models taxa counts with a negative binomial model. To look specifically at before and after FMT, we will apply multivariate techniques such as principal coordinate analysis (PCoA) to identify parameters that are affected positively by FMT and to determine whether these differences persist over time. The PERMNOVA technique will be applied to survey population-level differences before \& after FMT. We will use the Benjamini-Hochberg false discovery rate (FDR) to account for multiple hypothesis testing.
Time frame: Up to 6 months
GvHD improvement
Clinical efficacy will be defined as \> 50% of subjects with at least 1 stage of gut GvHD improvement by 8 weeks after the first dose of FMT.
Time frame: Up to 8 weeks after the first dose of FMT
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