Fecal Microbiota Transplantation for Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Fred Hutchinson Cancer Center
Must be taking: Calcineurin inhibitors, Methotrexate
Must not be taking: Antibiotics
Disqualifiers: Severe food allergy, Chronic aspiration, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but it does require stopping antibacterial antibiotics (except for certain preventive ones) for 2 days before randomization. You can continue taking prophylactic antiviral and antifungal medications.
What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Graft-versus-Host Disease?
Research shows that Fecal Microbiota Transplantation (FMT) can help restore healthy gut bacteria in patients with graft-versus-host disease (GVHD), with studies reporting an overall response rate of 82.4% in terms of complete and partial remission. FMT appears to be a safe and promising treatment option, although more research is needed to establish it as a standard care.
12345Is fecal microbiota transplantation (FMT) safe for humans?
Fecal microbiota transplantation (FMT) has been shown to be generally safe in humans, with studies indicating it is well-tolerated and associated with few significant adverse events. It has been used safely for conditions like Clostridioides difficile infection and has shown promise in other diseases, with some reports of mild side effects such as abdominal pain.
12678How is fecal microbiota transplantation different from other treatments for graft-versus-host disease?
Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore the balance of gut bacteria, which can help treat graft-versus-host disease by improving the gut microbiome. Unlike traditional treatments, FMT uses oral capsules or other methods to deliver beneficial bacteria directly to the gut, offering a novel approach to managing this condition.
136910Eligibility Criteria
Adults undergoing allogeneic hematopoietic cell transplantation for blood cancers can join this trial. They must be able to swallow capsules, not pregnant or breastfeeding, willing to use contraception, and have no severe food allergies or chronic aspiration. Participants should not be on other experimental GVHD prevention agents.Inclusion Criteria
You are committed to employing a recognized form of contraception for 180 days following the transplant and will refrain from donating eggs/sperm during that period.
I have not had severe acute graft-versus-host disease.
I can take pills by mouth.
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Exclusion Criteria
You have a severe food allergy that causes a dangerous reaction or requires you to be hospitalized.
You have a history of frequently inhaling food or liquid into your lungs.
You are currently taking or planning to take other experimental drugs to prevent a condition called GVHD.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive fecal microbiota capsules or placebo orally once daily for 7 days starting at the time of neutrophil engraftment and discontinuation of anti-bacterial antibiotics
1 week
Daily visits (in-person or virtual)
Follow-up
Participants are monitored monthly for safety and effectiveness after treatment until 12 months post-allogeneic HCT
12 months
Monthly visits (in-person)
Participant Groups
The study is testing if swallowing fecal microbiota transplantation capsules can prevent severe acute graft versus host disease after a transplant. Half the participants will receive these capsules and half will get a placebo, chosen randomly.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Group I (fecal microbiota transplant)Experimental Treatment1 Intervention
Patients receive fecal microbiota capsules PO QD for 7 days
Group II: Group II (Placebo)Placebo Group1 Intervention
Patients receive placebo PO QD for 7 days
Fecal Microbiota Transplantation Capsule is already approved in United States for the following indications:
🇺🇸 Approved in United States as Rebyota for:
- Prevention of recurrent Clostridioides difficile infection (CDI) in adults 18 years and older who have completed antibiotic treatment for recurrent CDI
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
Fred Hutchinson Cancer CenterLead Sponsor
References
[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety]. [2020]Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD).
Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. [2023]We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.
Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease. [2021]The growing understanding of the bidirectional relationship between the gastrointestinal (GI) microbiome and the immune system has opened up new avenues for treatment of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) is the transfer of stool from a donor to a recipient who harbors a perturbed GI microbiome resulting in disease. We review the rationale for performing FMT for the treatment of acute GVHD, and summarize data on the safety and efficacy of the procedure among allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Overall, FMT is a promising strategy in treating and preventing HSCT-related complications. However, caution should be exerted as HSCT recipients are highly immunosuppressed and unanticipated infectious adverse events may appear with the increasing application of FMT.
Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease. [2022]A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.
Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial. [2023]Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.
Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report. [2022]Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.
The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey. [2022]Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.
Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. [2021]Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.
[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.
Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [2020]Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.