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

Primary Purpose

Fecal Microbiota Transplantation in GVHD

Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation
Sponsored by
Shanghai Children's Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fecal Microbiota Transplantation in GVHD focused on measuring FMT, GVHD, HSCT

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    HSCT patients with refractory GVHD

    Arm Description

    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).

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    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.
    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.
    Implantation rate
    The data will be compared with patients who had not participated in clinical trials.
    Survival rate
    The data will be compared with patients who had not participated in clinical trials.
    Change in biomarkers
    Change in levels of albumin and C-reactive protein between days 0 and days 28 will serve as a secondary endpoint.
    Number of patients with infectious disorders
    Evaluation of FMT activity on infectious disorder.
    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.

    Full Information

    First Posted
    May 15, 2018
    Last Updated
    March 22, 2019
    Sponsor
    Shanghai Children's Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03549676
    Brief Title
    Fecal Microbiota Transplantation for Treatment of Refractory Graft Versus Host Disease-a Pilot Study
    Official Title
    Fecal Microbiota Transplantation for Treatment of Refractory Graft Versus Host Disease-a Pilot Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    July 1, 2019 (Anticipated)
    Primary Completion Date
    May 31, 2020 (Anticipated)
    Study Completion Date
    December 31, 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Shanghai Children's Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Fecal Microbiota Transplantation in GVHD
    Keywords
    FMT, GVHD, HSCT

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    15 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    HSCT patients with refractory GVHD
    Arm Type
    Experimental
    Arm Description
    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).
    Intervention Type
    Biological
    Intervention Name(s)
    Fecal Microbiota Transplantation
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Efficacy of FMT in the treatment of refractory GVHD on day 7
    Description
    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.
    Time Frame
    7 days following FMT
    Title
    Efficacy of FMT in the treatment of refractory GVHD on day 28
    Description
    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.
    Time Frame
    28 days following FMT
    Secondary Outcome Measure Information:
    Title
    Treatment-related AEs and SAEs
    Description
    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.
    Time Frame
    up to 28 days following FMT
    Title
    GVHD severity
    Description
    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.
    Time Frame
    up to 28 days following FMT
    Title
    Implantation rate
    Description
    The data will be compared with patients who had not participated in clinical trials.
    Time Frame
    through study completion, an average of 6 months
    Title
    Survival rate
    Description
    The data will be compared with patients who had not participated in clinical trials.
    Time Frame
    through study completion, an average of 6 months
    Title
    Change in biomarkers
    Description
    Change in levels of albumin and C-reactive protein between days 0 and days 28 will serve as a secondary endpoint.
    Time Frame
    up to 28 days following FMT
    Title
    Number of patients with infectious disorders
    Description
    Evaluation of FMT activity on infectious disorder.
    Time Frame
    through study completion, an average of 6 months
    Title
    Quality of Life
    Description
    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.
    Time Frame
    up to 6 months following FMT

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Qing Cao, MD
    Phone
    +86 18930830511
    Email
    caoqing@scmc.com.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yue Tao, PhD
    Phone
    +86 15121067906
    Email
    taoyue@scmc.com.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Qing Cao, MD
    Organizational Affiliation
    Shanghai Children's Medical Center
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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