Fecal Microbiota Transplantation in GVHD
Conditions
Keywords
FMT, GVHD, HSCT
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.
Interventions
BIOLOGICALFecal 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.
Sponsors
Shanghai Children's Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of FMT in the treatment of refractory GVHD on day 7 | 7 days following FMT | 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 | 28 days following FMT | 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
| Measure | Time frame | Description |
|---|---|---|
| Implantation rate | through study completion, an average of 6 months | The data will be compared with patients who had not participated in clinical trials. |
| Survival rate | through study completion, an average of 6 months | The data will be compared with patients who had not participated in clinical trials. |
| Treatment-related AEs and SAEs | up to 28 days following FMT | 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. |
| Number of patients with infectious disorders | through study completion, an average of 6 months | Evaluation of FMT activity on infectious disorder. |
| Quality of Life | up to 6 months following FMT | 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. |
| Change in biomarkers | up to 28 days following FMT | Change in levels of albumin and C-reactive protein between days 0 and days 28 will serve as a secondary endpoint. |
| GVHD severity | up to 28 days following FMT | 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. |
Contacts
Primary ContactQing Cao, MD
Backup ContactYue Tao, PhD
Outcome results
None listed