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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether capsules filled with healthy gut bacteria (from fecal matter) can prevent graft-versus-host disease (GVHD) in individuals who have undergone a specific type of stem cell transplant. GVHD occurs when transplanted cells attack the body, and the trial aims to determine if these capsules can prevent this. Participants will receive either the gut bacteria capsules, known as Fecal Microbiota Transplantation Capsules, or a placebo for one week. This trial may suit those who have experienced GVHD after a transplant and can swallow capsules. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) is generally safe. In studies involving individuals with graft-versus-host disease, FMT was well-tolerated, with most participants experiencing no serious side effects. For example, one study found that many patients had positive outcomes without major issues. Another study demonstrated that FMT was safe for individuals with systemic lupus erythematosus, a different condition. The safety data from these studies suggest that FMT can be used without significant risk of harm. However, as this treatment is still under investigation, some risks might not yet be fully understood. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for graft-versus-host disease?

Unlike the standard treatments for graft-versus-host disease, which typically involve immunosuppressive drugs, fecal microbiota transplantation (FMT) uses beneficial bacteria from healthy donor stool to restore balance in the gut microbiome. This innovative approach offers the potential to modulate the immune response naturally, which could reduce inflammation and improve symptoms without the harsh side effects of traditional drugs. Additionally, FMT is administered through easy-to-take capsules, making it a convenient option compared to other more invasive procedures. Researchers are excited about this treatment because it represents a new way of addressing the root causes of the disease rather than just managing its symptoms.

What evidence suggests that fecal microbiota transplantation could be effective for preventing acute graft versus host disease?

Research has shown that fecal microbiota transplantation (FMT), which participants in this trial may receive, may help treat graft-versus-host disease (GVHD). In earlier studies, FMT restored a healthy balance of gut bacteria, crucial after certain stem cell transplants. For patients with chronic GVHD, FMT led to full or partial improvement in several cases, indicating its potential effectiveness. FMT has also proven beneficial in other conditions like systemic lupus erythematosus, enhancing its potential benefits. By reintroducing beneficial bacteria into the gut, FMT can help prevent serious issues like acute GVHD. ^{1 2 3 6 7}

Who Is on the Research Team?

Armin Rashidi

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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) 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40859356/

Fecal microbiota transplantation for refractory chronic graft ... Results: Among the 12 patients who underwent FMT, 1 patient achieved a complete response, and 5 patients achieved a partial response. Patients ...

2. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04336-z

Fecal microbiota transplantation for refractory chronic graft ... Fecal microbiota transplantation (FMT) was first demonstrated to be safe and effective in patients with systemic lupus erythematosus (SLE) [24].

3. nature.com nature.com/articles/s41467-025-56375-y

Fecal microbiota transplantation to prevent acute graft ... Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease. Article 27 September 2022. Introduction.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723012897

Fecal Microbiota Transplantation for Acute Graft-versus- ... Fecal microbiota transplantation (FMT) can achieve clinical responses in refractory GVHD, establishing the promise of microbiome-directed interventions in this ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39863610/

Fecal microbiota transplantation to prevent acute graft-versus ... FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06938165

Study Details | NCT06938165 | The Safety and Efficacy of ... This clinical study evaluates the safety and efficacy of fecal microbiota transplantation (FMT) in patients with steroid-refractory graft-versus-host disease ( ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123101716

Efficacy and Safety of Fecal Microbiota Transplantation in ... The present study indicates that FMT as a new potential therapy in the treatment of SR-cGvHD is safe, well tolerated, and effective.