Safety And Efficacy Of Fecal Microbiota Transplant In Gastrointestinal GVHD: A Multicentric Phase 2 Single-Arm Trial In India: SAFE-FMT Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- To assess safety of FMT as a treatment modality in adult patients developing steroid refractory or dependent acute gut GVHD
研究概览
简要总结
Rationale/Gaps in existing knowledge: Allogeneic hematopoietic stem cell transplant (alloHSCT) is an important therapeutic modality for multiple hematologicalconditions. Gastrointestinal Graft-versus-host-disease (gut GVHD) is an important life-threatening complication leading to significant morbidity and mortality (50-60%) in patients undergoing allo-HSCT. Survival outcomes of steroid refractory gut GVHD (SR-GVHD) and steroid dependent gut GVHD (SD-GVHD) continue to be dismal (20-30%).
Novelty of this study: Anecdotal reports indicate that FMT may be a potential treatment that is safe and effective in these conditions with response rates varying from 38-58%. Combination of FMT and ruxolitinib, which is the only approved second line therapy for SR-GVHD has produced overall responses of up to 71% (in a prospective single arm study).
Objectives: We now aim to investigate the safety of FMT systematically in SR-GVHD and SD-GVHD, through a multicenter phase 2 open-label single-arm trial, assessing safety (primary objective) and efficacy (secondary objective) of FMT combined with ruxolitinib. Methods: Fifteen patients meeting the inclusion criteria of the study will berecruited after consenting. One to 3 administrations of third-party fresh stools as per protocol will be delivered endoscopically. This will be combined with ruxolitinib which is the standard of care (SOC) treatment. We shall also be evaluating the change in gut microbiome (exploratory outcome) before and after FMT by performing next generation sequencing on the stool samples before and after the procedure.
Expected outcome: FMT is a safe modality of treatment in SR and SD gut GVHD.
This study has been approved by the ICMR in the small grant category (2025)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
To assess safety of FMT as a treatment modality in adult patients developing steroid refractory or dependent acute gut GVHD
时间窗: 7 days, 14 days, 28 days, 3 months from inclusion into the trial
次要结局
- 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 trial(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 Response(Overall response at 3 months [Overall gut GVHD response - Sum of CR, VGPR and partial response (PR) rates])
- Duration of response (DOR)(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 procedure(After each FMT and at 3 months)
研究者
Shouriyo Ghosh
Tata Medical Center, Kolkata