Pilot Study of Fecal Microbiota Transplantation in Combination With Ruxolitinib and Steroids for Severe Acute Intestinal Graft-versus-host-disease After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
Therapy of severe intestinal graft-versus-host disease (GVHD) despite the introduction of novel target agents is associated with worse outcome compared to the other forms. Response to steroids is observed only in about 10% of patients. The most promising approaches are JAK inhibition and fecal microbiota transplantation. In this pilot study we evaluate this combination treatment in the first line.
详细描述
Acute intestinal GVHD grade III-IV after allogeneic stem cell transplantation the form with low effectiveness of corticosteroids. Despite high response rate to systemic immunosupressive agents, long term survival in this group is poor due to recurrent septic episodes and gut colonization with multidrug resistant bacteria. Fecal microbiota transplantation (FMT) from a healthy allogeneic donor, allows to restore numerous local and systemic microbiota functions, including immunomodulation and thus to reduce/stop the manifestations of GVHD. The therapeutic mechanism of action of FMT is based on competition for nutrients between obligate and pathologic bacterial strains, direct growth inhibition of the pathological pathogens, host immune system modulation, especially T-reg homeostasis, through interaction with the normal microbiota.In this pilot trial we combine FMT with ruxolitinib and steroids, one of the most effective option for refractory GVHD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 5-70 years
- •Histologically confirmed gastrointestinal acute GVHD
- •Grade III-IV gastrointestinal GVHD based on 2016 MAGIC criteria
- •Ability for oral drug intake
- •Signed informed consent
排除标准
- •Requirement for oxigen and/or vasopressor support
- •Respiratory distress >grade I
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits,creatinine clearance < 60 mL/min
- •Ongoing fluconazole therapy
- •Any malignancy requiring systemic therapy at the time of enrollment
- •Mixed chimerism at last evaluation
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <30%
- •Severe concurrent illness that can interfere with study procedures
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
研究组 & 干预措施
FMT+ruxolitinib+steroids
ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid
干预措施: allogeneic fecal microbiota (Biological)
FMT+ruxolitinib+steroids
ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid
干预措施: Ruxolitinib (Drug)
FMT+ruxolitinib+steroids
ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid
干预措施: Methylprednisone (Drug)
结局指标
主要结局
Overall survival
时间窗: 365 days
Time from treatment initiation to death or end of follow up
次要结局
- Time to ruxolitinib discontinuation(365 days)
- Time to systemic immunosuppression discontinuation(365 days)
- Infectious complications(100 days)
- Incidence of Adverse Events based on CTC AE 5.0(100 days)
- Time to steroid discontinuation(100 days)
- Overal response rate(100 days)
研究者
Ivan S Moiseev
Deputy Director for research, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation Affiliation: St. Petersburg State Pavlov Medical University
St. Petersburg State Pavlov Medical University