Fecal Microbiota Transplantation in aGvHD After ASCT

Study Overview
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Brief Summary
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Acute graft-versus-host-disease (aGvHD) is a typical complication after allogeneic hematopoetic stem cell transplantation (ASCT). About 30-60% of patients after ASCT are affected by aGvHD, which constitutes a relevant burden of morbidity and mortality in these patients. Fecal microbiota transplantation (FMT) is a therapeutic concept to treat intestinal dysbiosis of various origin by infusion of the stool microbiota of a healthy donor into the gastrointestinal tract (GI) of a patient. FMT can be performed endoscopically by colonoscopic deployment of the donor microbiota into the patient´s caecum and terminal ileum. Patients with gastrointestinal aGvHD (GI-aGvHD) are known to comprise a significant dysbiotic colonic microbiota that can be attenuated by FMT.

Official Title
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Fecal Microbiota Transplantation in Patients With Acute Gastrointestinal Graft-versus-host-disease After Allogeneic Stem Cell Transplantation

Conditions
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Graft Versus Host Disease in GI Tract

Intervention / Treatment
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* Biological: Fecal microbiota transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first episode of histologically confirmed, steroid-refractory GI-aGvHD reduced bacterial diversity in the patient´s stool microbiota evidenced by 16s-rDNA measurement eligibility for repeated colonoscopic procedures informed consent Exclusion Criteria: complications during a previous colonoscopy recurrent episode of GI-aGvHD lacking cardiopulmonary fitness for repeated colonoscopic procedures septic infection acute extraintestinal organ failure (excluding bone marrow) mechanical ileus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Patients with acute gastrointestinal graft-versus-host disease refractory to steroid treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Steroid refractory GI-aGvHD<br>Patients with GI-aGvHD not sufficiently responding to GvHD therapy with corticosteroids. Intervention: Fecal microbiota transplantation | Biological: Fecal microbiota transplantation<br>* 200 ml of a tested stool suspension of a healthy donor is instilled into the patient´s caecum or terminal ileum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI-aGvHD remission | Sustained remission of GI-aGvHD (CR or PR) | 90 days after first FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI-aGvHD remission | Sustained remission of GI-aGvHD (CR or PR) | 45, 180 and 365 days after first FMT | 
| Disease-free survival | GI-aGvHD free survival | 180 and 365 days after first FMT | 
| Recurrence of GI-GvHD | Recurrence of GI-GvHD | 365 days after remission | 
| Patient survival | Survival (death or alive) | 180 and 365 days after first FMT | 
| SUSAR (Suspected Unexpected Serious Adverse Reaction) | Number of lethal or non-lethal SUSAR's | within 48 hours after a FMT | 
| SAE (Serious Adverse Event) | Number of lethal or non-lethal SAE's | within 48 hours after a FMT |