Fecal Microbiota Transplantation for Steroid Resistant/Dependent Acute GI GVHD

Phase 2

Completed

• Conditions: Hematopoietic and Lymphoid Cell Neoplasm
• Interventions: Biological: fecal microbiome transplantation

• Registration Number: NCT03812705
• Lead Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of fecal microbiome transplantation in patients with steroid resistant/dependent acute gastrointestinal graft-versus-host disease (GVHD). The patient will cease antibiotics treatment 1 day before FMT, and stop taking food 6 hours before FMT. Patients will be given Ondansetron intravenously 1 hour before FMT. Patients will be injected 200\~300 ml fecal microbiome fluid to left colon by Colonoscopy or duodenum through duodenal tube by gastroscopy. If patient's condition is stable or improved within 1 week, second FMT may be performed 1 week later, up to 4 times will be performed if patient response. If patient's condition is not improved after the second FMT, ceasing FMT.

Detailed Description

The purpose of this study is to evaluate the efficacy and safety of fecal microbiome transplantation in patients with steroid resistant/dependent acute gastrointestinal graft-versus-host disease (GVHD).

Inclusion criteria:

1. Age\>= 14 yrs ≤60 yrs.

2. Diagnosed with hematological diseases.

3. Recipients of allogeneic peripheral blood stem cell transplantation.

4. Steroid resistant/dependent acute intestinal graft-versus-host disease (GVHD) within 100 days post-transplantation. The definition of steroid resistant/dependent acute intestinal GVHD is progression within 3 days of starting treatment or an incomplete response by 7 days or recurrence after initial dose reduction.

5. ECOG score ≤2;

6. signed consent form.

Exclusion criteria:

1. Complicated with uncontrolled severe infection except intestine and colon.

2. High risk of hemorrhage, dysfunction of coagulation, active gastrointestinal hemorrhage;

3. Absolute neutrophil count (ANC) \<0.5×10e9/L or platelet count (PLT) \< 20×10e9/L

4. Severe organ dysfunction, including heart failure, respiratory failure, renal failure, epilepsy or central nervous system dysfunction.

5. Participating other clinical trials.

6. Pregnant women.

Treatment:

1. Stop antibiotics treatment 1 day before FMT;

2. Fasting food 6 hours before FMT;

3. Give Ondansetron intravenously 1 hour before FMT for vomiting prevention;

4. Injection of 200\~300 ml fecal microbiome fluid to left colon by Colonoscopy or duodenum through duodenum tube by gastroscopy;

5. If patient's condition is stable or improved within 1 week, second FMT may be performed 1 week later, up to 4 times will be performed if patient response;

6. If patient's condition is not improved after the second FMT, stop FMT.

Major endpoint Response rate of acute gastrointestinal GVHD with 12 weeks after FMT, including complete response and partial response.

Minor endpoints:

1. Time to response of acute gastrointestinal GVHD;

2. Duration of response of acute gastrointestinal GVHD.

Study Timeline

• Study Start: 2018-12-13
• Study First Submitted: 2019-01-19
• Study First Submitted QC: 2019-01-19
• Study First Posted: 2019-01-23
• Primary Completion: 2024-03-30
• Status Verified: 2024-04
• Study Completion: 2024-04-15
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Age>= 14 yrs ≤60 yrs.
2. Diagnosed with hematological diseases.
3. Recipients of allogeneic peripheral blood stem cell transplantation.
4. Steroid resistant/dependent acute intestinal graft-versus-host disease (GVHD) within 100 days post-transplantation. The definition of steroid resistant/dependent acute intestinal GVHD is progression within 3 days of starting treatment or an incomplete response by 7 days or recurrence after initial dose reduction.
5. Eastern Cooperative Oncology Group (ECOG) score ≤2;
6. Signed consent form.

Exclusion Criteria

1. Complicated with uncontrolled severe infection except intestine and colon.
2. High risk of hemorrhage, dysfunction of coagulation, active gastrointestinal hemorrhage;
3. Absolute neutrophil count (ANC) <0.5×10e9/L or platelet count (PLT) < 20×10e9/L
4. Severe organ dysfunction, including heart failure, respiratory failure, renal failure, epilepsy or central nervous system dysfunction.
5. Participating other clinical trials.
6. Pregnant women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
fecal microbiome transplantation	fecal microbiome transplantation	1. Perform fecal microbiome transplantation to patient under colonoscopy or gastroscopy: injection of 200\~300 ml fecal microbiome fluid as fecal microbiome transplantation to left colon by Colonoscopy or duodenum through duodenum tube by gastroscopy; 2. If patient's condition is stable or improved within 1 week, second fecal microbiome transplantation may be performed 1 week later, up to 4 times will be performed if patient response; 3. If patient's condition is not improved after the second fecal microbiome transplantation, stop fecal microbiome transplantation.

Primary Outcome Measures

Name	Time	Method
Response rate	12 weeks within FMT	Response rate of acute gastrointestinal GVHD after FMT, including complete response and partial response.

Secondary Outcome Measures

Name	Time	Method
Duration of response	12 weeks within FMT	Duration of response of acute gastrointestinal GVHD
Time to response	12 weeks within FMT	Time to response of acute gastrointestinal GVHD

Trial Locations

Locations (2)

Shanghai Jiao Tong University Affilated First People's Hospital; 🇨🇳 Shanghai, Shanghai, China

Shanghai Jiao Tong University Affilated Shanghai General Hospital; 🇨🇳 Shanghai, Shanghai, China