This phase I trial studies how well fecal microbiota transplant and dietary fiber supplementation work in treating patients with gut graft versus host disease. Fecal microbiota transplant entails inoculating donor stool into a recipient's gastrointestinal tract. Changing the gut microbiome by fecal microbiota transplant and fiber supplementation may help treat gut graft versus host disease.
18 years of age or older
History of allogeneic hematopoietic stem cell transplant in the past 365 days
Post-engraftment, defined by time period following three consecutive days of sustained neutrophil engraftment with an absolute neutrophil count of at least 500 cells/mm^3
Modified Glucksberg criteria for GI GvHD averaged over 3 consecutive days and without another explanation for diarrhea such as laxative use or infection. In patients who have already had GI biopsy, biopsy histology must be compatible with GVHD, although biopsy is not required
History of previous serious adverse events associated with FMT
History of bowel perforation in the last 90 days
History of gastrointestinal resection in the last 90 days
History of small bowel obstruction without surgical intervention in the last 30 days, or 90 days with surgery, or history of large bowel obstruction in last 90 days
Parallel
Colonoscopy
Procedure/SurgeryUndergo lower FMT via colonoscopy
Fecal Microbiota Transplantation
Biological/VaccineGiven upper FMT PO or via post-pyloric or NG feeding tube
Fecal Microbiota Transplantation
Biological/VaccineUndergo lower FMT via colonoscopy
Nutritional Supplementation
Dietary supplementGiven dietary fiber supplementation PO or via post-pyloric or NG feeding tube
Survey Administration
Other interventionAncillary studies
Biospecimen Collection
Procedure/SurgeryUndergo tissue, stool, stool swabs, and blood sample collection
Bacterial composition of stool
Analyses will consist of summary statistics of the bacterial diversity in the microbiome (e.g., the alpha diversity, the abundance of bacterial species associated with protection from graft versus host disease \[GvHD\]).
Bacterial genes in stool
Specifically abundance of genes related to fiber fermentation and short chain fatty acids production metabolites in stool, specifically short chain fatty acids will be assessed.
Incidence of adverse events
Will by assessed by computing the total number of adverse events (AE)s and serious adverse events (SAE)s, the number per patient, and the number of patients with at least one event. The type of AE/SAE and whether the AE/SAE is related to the fecal microbiota transplant (FMT) or not will be tabulated. These summaries will be computed overall as well as by randomization arm and stratification factor (steroid-responsive, versus steroid-dependent or -refractory disease status). The odds will be compared of at least one SAE per patient by randomization arm and stratification factor using logistic regression with independent variables for route of FMT administration, fiber supplementation, and steroid-responsive, versus steroid-dependent or -refractory disease status. Interaction terms will be considered between these factors and may use exact or firth logistic regression in the event that some categories have zero patients with a SAE.
Complete response (CR) after the initial FMT
Will be defined by stage 0 on the Modified Glucksberg GvHD scale, without abdominal pain or hematochezia. To account for variability in this measure, patient stool volume (inpatients only) and survey data (both inpatients and outpatients) from days 25-27 will be used to determine whether patients meet these criteria or not. Inpatients will be a compare measured stool volumes to those reported via survey, to assess how well the survey data may serve as a surrogate for stool volume. Subjects who die before day 28 will be counted as no CR. The number and proportion of patients with CR by steroid-responsive, versus steroid-dependent or -refractory disease status, and each randomization arm (route of FMT administration and receipt of fiber supplementation) as well as within combinations of these factors will be computed. To test for differences in CR by these factors, logistic regression models similar to those described above for SAE comparisons.
CR or partial response (PR) after the initial FMT
Will be assessed by CR or PR at day 28 will use similar analysis methods as to the CR at day 28 outcome analysis.
Gut and overall GvHD grade
Will be assessed using the Modified Glucksberg scale measurements at baseline and throughout follow-up to summarize decrease in stool volume. For both of these ordinal outcomes (GvHD grade and Modified Glucksberg scale stage), descriptive statistics and graphical summaries to show changes over time by stratification factor and randomization arm. Generalized linear mixed effects models to test for differences in these outcomes by stratification factor and randomization arm.
Six-month survival
Will be evaluated using Kaplan-Meier curves and Cox proportional hazards regression with independent variables for the steroid- responsive, versus steroid-dependent or - refractory disease and randomization arm as specified in previous models.
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Fred Hutchinson Cancer Center
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
