Health Condition 1: Z948- Other transplanted organ and tissue status
Conditions
Interventions
Intervention1: Fecal Microbiota Transplant: 1 to 3 administrations of third-party fresh stools as per protocol delivered endoscopically. This will be combined with Standard of care (SOC) treatment. Du
Sponsors
Indian Council of Medical Research
Eligibility
Inclusion criteria
Inclusion criteria: Age more than or equal to 18 years old Allo-HSCT with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen Classic onset Gastro-Intestinal Acute GVHD, fulfilling all the 4 requirements Less than 100 days from allo-HSCT GI aGVHD Grade II to IV (MAGIC Criteria) Gut predominance, if other organs involved: MAGIC grading for lower GI GVHD must be higher than the grading of any other organ involved. Histopathological evidence of diagnosis (probable, possible or definite evidence of gut GVHD) iOne of the 2 following statuses: Corticosteroid-refractory GI-aGVHD, defined as: Progression within 3 days of therapy onset with 1-2 mg/kg/day of methylprednisolone OR Failure to improve within 5-7 days of treatment initiation. Corticosteroid-dependent GI-aGVHD, defined as: Recurrence of aGVHD activity during steroid taper Controlled hematological malignant disease. Signed informed and written consent by the subject or by the subject s legally acceptable representative Patients are able to have a minimum of 12 hours discontinuation of systemic antibiotics to perform FMT. For patients who require antibiotics, using antibiotics that have limited impact on the gut microbiota should be prioritized. The complete list of recommended and not recommended antibiotics is in Appendix 1.
Exclusion criteria
Exclusion criteria: Age less than 18 years old, Acute GVHD occurring after Donor Lymphocyte Infusion. Active uncontrolled infection according to the physician (except for minor infections such as skin and mucosal mycoses). Not able to discontinue antibiotics more than 12 hours before FMT. Known or past history of toxic megacolon, bowel obstruction or gastro-intestinal perforation, short bowel syndrome Absolute Neutrophil Count less than 0.5x106/ml. Relapsed/persistent malignancy requiring rapid immune suppression withdrawal Other ongoing interventional studies that might interfere with the current study s primary endpoint Evidence/risk of chronic aspiration Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess safety of FMT as a treatment modality in adult patients developing steroid refractory or dependent acute gut GVHDTimepoint: 7 days, 14 days, 28 days, 3 months from inclusion into the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficacy of the study cohort (FMT + ruxolitinib) in comparison to ruxolitinib alone at 28 days and 3 months after inclusion into the trialTimepoint: The secondary outcome measure will be gastrointestinal response (GI) response at 28 days after inclusion. GI response will be categorized as the sum of complete response (CR) and very good partial response (VGPR) rates. The efficacy analysis will be done by comparing this group with a matched cohort of retrospective patients from both participating centers, treated with ruxolitinib alone.;Overall ResponseTimepoint: Overall response at 3 months [Overall gut GVHD response - Sum of CR, VGPR and partial response (PR) rates];Duration of response (DOR)Timepoint: End of study;3. Exploratory objective: Assessment of a microbiota signature to study the impact of FMT on the reconstitution of the gut flora. This will be analyzed by next generation sequencing of the stool samples of the donor and the recipient at the following time points: prior to FMT, 7 days after each FMT procedure and at 3 months after the initial FMT procedureTimepoint: After each FMT and at 3 months | — |
Countries
India
Contacts
Public ContactShouriyo Ghosh
Tata Medical Center, Kolkata
Outcome results
None listed