Fecal Microbiota Transplantation for Graft-versus-Host Disease

Overseen By Armin Rashidi

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

138 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 2 6 7 8}

How 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. ^{1 3 6 9 10}

Research Team

Armin Rashidi

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility 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.

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.

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)

Treatment Details

Interventions

• Fecal Microbiota Transplantation Capsule
• Placebo

Trial Overview 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.

Participant Groups

Group I: Group I (fecal microbiota transplant) Experimental Treatment 1 Intervention

Patients receive fecal microbiota capsules PO QD for 7 days

Group II: Group II (Placebo) Placebo Group 1 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

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Findings from Research

Fecal microbiota transplantation (FMT) in 27 patients with gastrointestinal graft-versus-host disease (GVHD) showed significant clinical improvement, with a faster partial response compared to placebo (median 4 days vs 48 days).

FMT led to increased bacterial diversity and specific beneficial bacteria populations, such as Bifidobacterium and Bacteroides fragilis, without a higher incidence of severe adverse events, indicating it is a safe and effective treatment option for refractory GI GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety]. Goloshchapov, OV., Chukhlovin, AB., Bakin, EA., et al.[2020]

In a pilot study involving 18 subjects undergoing allogeneic hematopoietic cell transplantation (allo-HCT), third-party fecal microbiota transplantation (FMT) was found to be feasible and safe, with only one significant treatment-related adverse event reported (abdominal pain).

After FMT, there was a notable improvement in intestinal microbiome diversity, and the 12-month overall survival and progression-free survival rates were both 85%, indicating promising outcomes for patients receiving FMT post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. DeFilipp, Z., Peled, JU., Li, S., et al.[2023]

Fecal microbiota transplantation (FMT) shows promise as a treatment for acute graft-versus-host disease (GVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT), potentially improving outcomes related to HSCT complications.

While FMT can be beneficial, it must be approached with caution due to the high risk of infections in immunosuppressed HSCT recipients, highlighting the need for careful monitoring during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease. Shouval, R., Geva, M., Nagler, A., et al.[2021]

Fecal microbial transplantation (FMT) shows promise as a safe and effective intervention for managing graft-versus-host disease (GVHD), with an overall response rate of 82.4% based on data from 79 patients across six studies and five case reports.

While FMT resulted in complete remission in 55.9% and partial remission in 26.5% of patients, further randomized studies are needed to establish it as a standard treatment due to the small sample size and lack of direct prevention studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease. Alabdaljabar, MS., Aslam, HM., Veeraballi, S., et al.[2022]

In a post hoc analysis of a randomized phase II trial involving fecal microbiota transplantation (FMT) in patients after hematopoietic cell transplantation, higher donor microbiota engraftment was associated with a lower incidence of acute graft-versus-host disease (aGVHD), suggesting a protective effect of FMT.

Patients with more severe dysbiosis before FMT showed greater donor microbiota engraftment, indicating that FMT may be particularly beneficial for those with significant microbiota disruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial. Rashidi, A., Ebadi, M., Rehman, TU., et al.[2023]

Oral fecal microbiota transplantation (FMT) capsules were successfully used to treat a 31-year-old male with corticosteroid-refractory intestinal graft-versus-host disease (GvHD), leading to symptom relief and improved gut microbiota diversity after two treatment cycles.

Despite initial success, the patient's symptoms recurred after 11 days, highlighting the need for further research to optimize treatment protocols and assess the long-term efficacy and safety of oral FMT capsules in GvHD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report. Mao, D., Jiang, Q., Sun, Y., et al.[2022]

In 2019, 31 FMT centers across 17 European countries performed a total of 1,874 fecal microbiota transplants, primarily for Clostridioides difficile infection (CDI), indicating that FMT is a common treatment for this condition.

Despite the high safety standards and adherence to guidelines observed in these centers, only about 10% of the estimated patients needing FMT for recurrent CDI in Europe received the treatment, highlighting a significant gap in coverage and the need for increased clinical awareness and activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey. Baunwall, SMD., Terveer, EM., Dahlerup, JF., et al.[2022]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for Clostridioides difficile infection, and emerging evidence suggests it may also benefit various other conditions like irritable bowel syndrome and inflammatory bowel disease.

The review highlights the expanding applications of FMT beyond gastrointestinal issues, including its potential roles in treating liver disorders, metabolic disorders, and even neurological conditions, while also discussing regulatory aspects and future directions for FMT research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. Ianiro, G., Segal, JP., Mullish, BH., et al.[2021]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridioides difficile infection (CDI), achieving resolution rates close to 100%, making it a crucial therapy for this serious condition.

FMT is being explored as a promising treatment for other gastrointestinal disorders, such as inflammatory bowel disease, irritable bowel syndrome, and colon cancer, due to its ability to manipulate the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. Borody, TJ., Eslick, GD., Clancy, RL.[2020]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety]. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. [2021]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [2020]