Fecal Microbiota Transplantation for Treatment of Refractory Graft Versus Host Disease-a Pilot Study

Study Overview
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Brief Summary
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The study evaluates safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of refractory graft-versus-host-disease (GVHD) of the gut. FMT might be a beneficial treatment in this clinical situation with a poor prognosis and limited therapeutic options.

Detailed Description
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Graft-versus-host-disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT). Gut is the most vulnerable target organ of acute GVHD. Patients who have a gastrointestinal acute GVHD received a first-line standard treatment of corticosteroids. For patients who do not respond or progress after an initial response have a high mortality. Therefore, the investigation of effective second line therapy for these patients are in need. The study evaluates safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of refractory GVHD of the gut. FMT might be a beneficial treatment in this clinical situation with a poor prognosis and limited therapeutic options.

Official Title
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Fecal Microbiota Transplantation for Treatment of Refractory Graft Versus Host Disease-a Pilot Study

Conditions
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Fecal Microbiota Transplantation in GVHD

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 3-18 years of age Allo-SCT patients with acute steroid-resistant GI-related GVHD grade III-IV. Steroid-resistant GI-related GVHD will be defined as lack of improvement (same stage) or worsening of GI symptoms after 7 days of steroid therapy (≥ 2 ml/kg of IV methylprednisolone) No definite contraindication for gastrointestinal endoscopy Signature of informed consent by the legal guardians of patients Exclusion Criteria: Prior inclusion to an interventional study Previous Allo-SCT Known multi-drug resistance carriage prior to stool collection Severe colitis of any etiology or a history of inflammatory bowel disease (IBD) Uncontrolled infection (hemodynamic instability, ongoing high fever or bacteremia within 3 days after antibiotics administration) Active GI bleeding Absolute neutrophil count < 500 cells/microL Absolute platelet count< 10 x 109 /L Patients who cannot give informed consent

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSCT patients with refractory GVHD<br>Patients will accept FilmArray Gastrointestinal (GI) panel test before pre-treatment of HSCT and 28±3 days post-HSCT. Patients will receive 50ml fecal microbiota from unrelated healthy donors through nasojejunal tube and monitored under gastroscopy. Patients receiving FMT treatment will be followed for at least 6 months. The ideal follow up time is 2 year. Stool and blood samples will be serially collected and tested (before pre-treatment, 1/3/6/12 months after FMT). | Biological: Fecal Microbiota Transplantation<br>* For patients who do not respond or partial respond for first time FMT treatment, a second time FMT treatment using different donor should be considered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of FMT in the treatment of refractory GVHD on day 7 | Participants will be evaluated on days 7 following FMT. The volume and frequency of daily diarrhoea will be continuous observed and recorded in 7 days. | 7 days following FMT | 
| Efficacy of FMT in the treatment of refractory GVHD on day 28 | Participants will be evaluated on days 28 following FMT. The volume and frequency of daily diarrhoea will be continuous observed and recorded in 28 days. | 28 days following FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related AEs and SAEs | The overall safety of the study will be evaluated with the incidence of all Adverse Events (AEs) and Serious Adverse Events (SAEs) within 28 days following FMT. The relationship of any kind AEs and FMT will be seriously evaluated. Non-serious AEs include: dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, fever, inhalation without mechanical ventilation, etc. SAEs include: death, sepsis, aspiration pneumonia, gastrointestinal hemorrhage, septic shock, etc. | up to 28 days following FMT | 
| GVHD severity | Patients will be evaluated on days 7 and 28 following transplantation for severity of GVHD. GVHD severity is graded by the International Bone Marrow Transplant Registry Severity Index grading system. | up to 28 days following FMT | 
| Implantation rate | The data will be compared with patients who had not participated in clinical trials. | through study completion, an average of 6 months | 
| Survival rate | The data will be compared with patients who had not participated in clinical trials. | through study completion, an average of 6 months | 
| Change in biomarkers | Change in levels of albumin and C-reactive protein between days 0 and days 28 will serve as a secondary endpoint. | up to 28 days following FMT | 
| Number of patients with infectious disorders | Evaluation of FMT activity on infectious disorder. | through study completion, an average of 6 months | 
| Quality of Life | The quality of life of patients will be measured using a standardized quality of life questionnaire (EORTC QLQ-C30) prior to transplantation and on days 7, 14, 21, 28 and 180 following transplantation. | up to 6 months following FMT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FMT, GVHD, HSCT