Randomized Phase II Trial of Total Gut Decontamination Followed by Fecal Microbiota Transplant (FMT), FMT-Alone or Standard of Care for Reduction in Acute Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients Given Broad-Spectrum Antibiotics
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Development of acute gastrointestinal (GI) graft versus host disease (GVHD)
研究概览
简要总结
This phase II trial studies how well a fecal microbiota transplant with or without total gut decontamination works in preventing graft versus host disease in patients exposed to broad-spectrum antibiotics. Fecal microbiota transplantation is the administration by enema of fecal matter (stool) that includes helpful bacteria from a normal, healthy donor. Total gut decontamination uses antibiotics to remove/reduce the amount of bacteria in the digestive system. It is not yet known if a fecal microbiota transplant with or without total gut decontamination works better in preventing graft versus host disease compared to standard immunosuppressive therapies (therapies that lower the normal function of the immune system).
详细描述
PRIMARY OBJECTIVES:
I. To estimate the proportion of patients who develop acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract by day 100 post-transplant for patients randomized to the standard of care, total gut decontamination (TGD) followed by fecal microbiota transplant (fecal microbiota transplantation [FMT]) and FMT alone arms.
SECONDARY OBJECTIVES:
I. Overall maximum stage of lower GI tract GVHD by day 100 post-transplant. II. Cumulative incidence of acute GVHD grade II-IV and maximum grade through 6 months.
III. Time to onset of acute GVHD and acute GI GVHD. IV. Incidence of adverse events and serious adverse events. V. Incidence of bacterial blood stream infections through 6 months. VI. Hematologic recovery (neutrophils and platelets). VII. Characterization of the intestinal microbiota at enrollment, pre-FMT / time of engraftment, 2 month post-FMT/ engraftment, onset of gastrointestinal tract (GIT) GVHD, and at study completion (6 months).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are day -10 pre- to day +30 post-allogeneic hematopoietic cell transplant (AHCT) from any donor or graft source and for any conditioning regimen
- •Patients who have received treatment with meropenem or piperacillin-tazobactam (pip-tazo) intravenously (IV) (of at least 24 hours duration) in past 7 days
- •Controlled infection defined as hemodynamically stable and not requiring supplemental oxygen of more than 2 liters via nasal cannula
- •Patients who are able to take oral medications in suspension form
- •Patients who are able to provide informed consent (IC) and comply with all study visits and procedures
排除标准
- •Patients who are anticipated to require continued broad spectrum antibiotics with meropenem or pip-tazo IV for > 96 hours post-engraftment such as for known, documented infections necessitating prolonged treatment
- •Patients with a prior documented infection with mycormycetes
- •Patients who are greater than 2 days from time of neutrophil engraftment post AHCT
- •Patients with active enteric infections
- •Patients with acute GVHD >= grade II
- •Patients unwilling or unable to undergo the FMT via retention enema procedure
- •Patients who have received treatment with an investigational agent within 2 weeks of enrollment
- •Patients unable to tolerate oral decontamination regimen of pip-tazo and nystatin due to prior allergy or intolerance of these medications
- •Patients with any medical or psychological condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial, pose any additional risk for the subject, or confound the assessments of the subject
研究组 & 干预措施
Arm I (TGD + FMT)
Patients receive piperacillin-tazobactam PO TID and nystatin QID. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
干预措施: Fecal Microbiota Transplantation (Procedure)
Arm I (TGD + FMT)
Patients receive piperacillin-tazobactam PO TID and nystatin QID. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
干预措施: Nystatin (Drug)
Arm I (TGD + FMT)
Patients receive piperacillin-tazobactam PO TID and nystatin QID. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
干预措施: Piperacillin-Tazobactam (Drug)
Arm II (FMT)
Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
干预措施: Fecal Microbiota Transplantation (Procedure)
Arm III (standard therapy)
Patients receive standard of care.
干预措施: Best Practice (Other)
结局指标
主要结局
Development of acute gastrointestinal (GI) graft versus host disease (GVHD)
时间窗: Within 100 days from time of transplant
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Relapse-free survival
时间窗: At 6 months post-randomization
Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or myelodysplastic syndrome (MDS) inconstant with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The distribution of time-to-event endpoints, as well as the median and 90% confidence interval, will be estimated using the Kaplan-Meier method.
次要结局
- Microbiome diversity(At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm))
- Overall maximum stage of lower GI tract GVHD(Within 100 days post-transplant)
- Cumulative incidence of acute GVHD grade II-IV and maximum grade(Up to 6 months)
- Incidence of adverse and serious adverse events(Within 60 days of FMT)
- Incidence of bacterial blood stream infections(Up to 6 months)
- Hematologic recovery (neutrophils and platelets)(Up to 6 months)
- Characterization of the intestinal microbiota(Baseline up to 6 months)
- Non-relapse mortality(At 6 months post-randomization)
- Overall survival(At 6 months post-randomization)