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

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.

Study Overview

• Status: Unknown
• Conditions: Fecal Microbiota Transplantation in GVHD
• Intervention / Treatment: Biological: Fecal Microbiota Transplantation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: HSCT patients with refractory GVHD; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Children's Medical Center
• Investigators: Study Director: Qing Cao, MD, Shanghai Children's Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2019
• Primary Completion (ANTICIPATED): May 31, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (ACTUAL): June 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 22, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: FMT; GVHD; HSCT
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: FMT-GVHD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No