Autologous Fecal Microbiota Transplantation for Patients With Acute Graft-versus-Host Disease

Not Applicable

Withdrawn

• Conditions: Fecal Microbiota Transplantation in Graft vs. Host Disease
• Interventions: Biological: Autologous Fecal Microbiota Transplantation

• Registration Number: NCT03492502
• Lead Sponsor: Rambam Health Care Campus

Brief Summary

This study aims to assess the safety and efficacy of autologous fecal microbiota transplantation (FMT) in gastrointestinal (GI) related graft-versus-host disease (GVHD). Stool for FMT will be prepared from pre-allogeneic stem cell transplantation (Allo-SCT) period. This strategy might offer a novel and safe therapeutic approach for these patients, who suffer from high disease related morbidity and mortality and are refractory to multiple treatments.

Detailed Description

All candidates for Allo-SCT at BMT unit in RHCC will be screened for study inclusion and exclusion criteria. Seven to fourteen days prior to Allo-SCT (before initiation of SCT related antimicrobials), all consenting patients will supply stool sample (first stool sample), which will serve as the autologous FMT sample, and clinical data will be collected. Patients who will develop GI related GVHD will be asked to supply another stool sample 7±2 days after the appearance of GVHD related symptoms (second stool sample). Clinical and laboratory data will be collected. Another stool sample will be collected 7-14 following autologous FMT (third stool sample), and clinical data and outcome will be documented. Day 1 of the study will be defined as day of Allo-SCT, and follow up period is 6 months. Complementary data will be collected from the electronic medical records.

Study Timeline

• Study First Submitted: 2018-03-22
• Study First Submitted QC: 2018-04-07
• Study First Posted: 2018-04-10
• Study Start: 2019-08-01
• Status Verified: 2020-03
• Primary Completion: 2020-03-05
• Study Completion: 2020-03-05
• Last Update Submitted: 2020-03-09
• Last Update Posted: 2020-03-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

* Allo-SCT patients above 18 years of age with acute steroid-resistant GI-related GVHD grade III-IV.

Exclusion Criteria

• Prior inclusion to an interventional study
• Pregnant or lactating women
• 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 fever or bacteremia within 3 days after antibiotics administration)
• Active GI bleeding
• Absolute neutrophil count < 500 cells/microL
• Patients who cannot give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allo-SCT patients with GI related GVHD	Autologous Fecal Microbiota Transplantation	Allo-SCT patients above 18 years of age with acute steroid-resistant GI-related GVHD grade III-IV. The diagnosis of GVHD will be made on clinical grounds (in line with the major associations' recommendations) - the appearance of characteristic mucoid diarrhea within 100 days after Allo-SCT, with or without associated skin/liver involvement. In cases of atypical presentation - we will recommend biopsy or endoscopy for diagnosis. Patients suspected to have Clostridium difficille associated diarrhea will be tested for toxin (CDT). 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).

Primary Outcome Measures

Name	Time	Method
Development of severe adverse events (SAEs) related to autologous FMT	7 days	Development of SAEs related to autologous FMT within 7 days after the intervention. SAEs include mortality, bacteremia, and radiological-proven aspiration pneumonia requiring mechanical ventilation.

Secondary Outcome Measures

Name	Time	Method
Complete or partial response of GI-related GVHD after each FMT	90 days	Patients will be evaluated 90 days following FMT for symptoms severity and response. Response is defined as: 1. Complete response - resolution of all GI symptoms; 2. Partial response - decrease of severity of GI-related GVHD by at least one stage or ability to taper steroids to \<0.5 mg/kg; 3. No response - progression of symptoms or no change in GI symptoms
Non-severe adverse events (AE)	7 days	Non-severe adverse events including dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, fever, or aspiration not requiring mechanical ventilation. Each AE will be graded.
Mortality	90 days
Change in microbiota composition after each FMT	180 days

Trial Locations

Locations (1)

Rambam Health Care Campus; 🇮🇱 Haifa, Israel