Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute GVHD

Study Overview
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Brief Summary
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Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD) is a complication of allogeneic stem cell transplant which is usually treated with steroids. You are being asked to take part in this study because you have recently been diagnosed with GI-GVHD. The standard of care for GI-aGVHD is steroids. When aGVHD does not respond to steroids it is described as steroid-refractory aGVHD. There is no standard therapy for steroid-refractory GI-aGVHD. This study is a Phase II study. The main goal of a Phase II study is to see the efficacy and what side effects are seen with FMT as a treatment for GVHD. Fecal Microbiota Transplantation (FMT) is the transfer of fecal material from a healthy donor to a patient in order to restore the diversity of the intestinal microbiota. FMT is currently indicated for the treatment of recurrent Clostridium Difficile infection. FMT is considered experimental in this study, meaning it is not approved by the FDA for the treatment of GVHD.

Official Title
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Fecal Microbiota Transplantation For The Treatment Of Gastro-Intestinal Acute Graft Versus Host Disease

Conditions
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Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD)

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation (FMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following diagnosis: High risk aGVHD (either biopsy proven or clinical diagnosed) (see Appendix B & C) as defined by either: Lower gastrointestinal (GI) stage 3+ Hyper-acute GVHD as defined by aGVHD of the GI tract within the first 14 days of transplant AND Subjects with treatment-naive acute GVHD as defined as those who have not received previous systemic treatment for acute GVHD, except for a maximum of 7 days of no less than 1 mg/kg/day of methyl-prednisolone (or equivalent dose of prednisone). OR: Steroid refractory aGVHD of the GI tract (either biopsy proven or clinical diagnosed) as defined by: no response to steroid treatment (minimum daily dose: 2 mg/kg methyl-prednisolone or equivalent) lasting at least 7 days, or progression of at least one grade within the first 72 h of treatment ECOG Performance status < 3 Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source. Patients who are able stop prophylactic antibiotics during the treatment period Subjects must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Active malignancy Patients with any concurrent uncontrolled clinically significant medical condition including active infection, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment. Pregnant or breastfeeding women Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds Patients with any severe gastrointestinal condition other than GI-GVHD. Inability (e.g. dysphagia) to or unwilling to swallow capsules Active gastrointestinal infection at time of enrollment Known or suspected toxic megacolon and/or known small bowel ileus Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy History of total colectomy or bariatric surgery Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy Unable or unwilling to comply with protocol requirements Expected life expectancy < 6 months Patients who have CMV >2,000 copies/mL of whole blood or EBV >2,000 copies/mL of whole blood.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The study follows R. Simon's minimax two-stage phase II design with type I error of 0.05 and power of 80%. Ten participants will be enrolled on stage one. If there are 2 or less responses, the trial will be stopped and the treatment will be considered less than 60% effective for this patient population. If there are 3 or more responses, 7 additional patients will be enrolled.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation (FMT)<br>One dose of FMT equal to 30 capsules will be administered on day 1 of a 28 day cycle. Steroids and routine GVHD prophylaxis medications and antibiotics may be administered concurrently with FMT therapy. Participants will be followed for 28 days following completion of the FMT dose or protocol defined outcome. aGVHD will be treated as per standard of care. | Biological: Fecal Microbiota Transplantation (FMT)<br>* 1 dose = 30 capsules on day 1 of Fecal Microbiota Transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing toxicity | Toxicity is defined as: Any bacterial or fungal infection that can be definitely attributed to FMT. Any grade 3 or more adverse event that occurs during or immediately after receiving the treatment and is definitely attributed to FMT. | up to 6 months from start of treatment | 
| Efficacy of FMT therapy in high risk and in steroid refractory GI-aGVHD as defined as number of responses at day 28 (+/- 3 days) post FMT treatment | Response will be determined from the maximum GI-aGVHD stage and grade at day 28 (+/- 3 days) post FMT treatment. Response will be determined by P.I and a second physician. Complete response (CR) is defined as the complete resolution of GI aGVHD symptoms, without secondary GVHD therapy. Partial response (PR) is defined as improvement without complete resolution and without worsening of GI aGVHD, without secondary aGVHD therapy. No response (NR) is defined as the same grade of GVHD, progression, death, or the addition of secondary GVHD therapy. Progression is defined as worsening GI aGVHD. | 28 days (+/- 3 days) post FMT treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse mortality (NRM) as measured by percentage of participants who die not related to relapse | Non-relapse mortality (NRM) as measured by percentage of participants who die not related to relapse | up to 6 months from start of treatment | 
| Relapse as measured by percentage of participants who relapse | Relapse as measured by percentage of participants who relapse | up to 6 months from start of treatment | 
| Relapse-related mortality as measured by percentage of participants with death related to relapse | Relapse-related mortality as measured by percentage of participants with death related to relapse. | up to 6 months from start of treatment | 
| Percentage of participants who develop cGVHD by the end of trial | Percentage of participants who develop cGVHD by the end of trial | up to 6 months from start of treatment | 
| Overall survival (OS) as measured by percentage of participants who are alive at end of trial | Overall survival (OS) as measured by percentage of participants who are alive at end of trial | up to 6 months from start of treatment | 
| Percentage of patients who discontinue steroids at the end of the study | Percentage of patients who discontinue steroids at the end of the study. | up to 6 months from start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft Versus Host Disease (GVHD)