A Randomized Phase 2 Study to Examine the Impact of Gut Decontamination on Intestinal Microbiome Composition in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Gut Microbiome Description
研究概览
简要总结
This research study is for participants who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and are at risk for developing acute graft-versus-host disease (GVHD). GVHD is a complication of HSCT in which immune cells from the donor cause inflammation and injury to tissues and organs of the HSCT recipient. Vancomycin-polymyxin B (commonly called "vancopoly") is an oral antibiotic that is given to people undergoing allogeneic HSCT as a preventive measure for acute GVHD. This research study is studying the effects of vancopoly on the microorganisms living in the intestine during and after stem cell transplantation.
详细描述
This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease.
"Investigational" means that the intervention is being studied.
Pre-clinical studies performed in the 1970's showed that killing all the bacteria in the intestine with oral antibiotics could decrease the risk of acute GVHD following allogeneic HSCT. Based on this observation, many stem cell transplant centers adopted the practice of "gut decontamination" with oral antibiotics as a preventive measure for acute GVHD. There is no standard regimen for gut decontamination between transplant centers, and there are no definitive human studies showing that gut decontamination is beneficial for lowering the risk of acute GVHD.
Recent studies in adult patients undergoing stem cell transplant indicate that the types of bacteria living in the intestine can influence bone marrow transplant outcomes such as survival and development of acute GVHD. Some types of bacteria may be protective against GVHD and others may increase the risk of GVHD. Based on this newer research, it is possible that the practice of gut decontamination ("vancopolys") may not be beneficial for HSCT patients.
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
- 4 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligibility Criteria for Patients Undergoing Allogeneic HSCT
- •Recipient of 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched bone marrow allogeneic hematopoietic stem cell transplantation (HSCT) OR 4/6, 5/6 and 6/6 (HLA-A, -B, -DR) matched cord blood allogeneic HSCT.
- •Participants may have underlying malignant or non-malignant hematologic disease, except for primary immunodeficiency, as the indication for their allogeneic HSCT. Patients with immune dysregulation such as familial or secondary hemophagocytic lymphohistiocytosis (HLH) are eligible.
- •Participants must may receive either a myeloablative or non-myeloablative(reduced-intensity) conditioning regimen. Anti-thymocyte globulin (ATG) in the conditioning regimen is permitted.
- •Graft-versus-host disease (GVHD) prophylaxis with any of the following agents: calcineurin inhibitor, and short-course methotrexate, with or without steroids, mycophenolate mofetil, and sirolimus.
- •Age ≥ 4 years old and toilet-trained. Participants must be able to deposit stool samples directly into stool collection containers. Stool specimens from diapers are difficult to obtain and are prone to more sampling error, particularly for loose or liquid stools which are common in the peri-transplant period.
- •Lansky/Karnofsky performance status ≥60% (see Appendix A)
- •Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document
- •Eligibility Criteria for Healthy Bone Marrow Donors
- •Healthy individuals, ages ≥ 4 years and toilet-trained, who have been identified by BCH or DFCI providers as 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1 matched bone marrow donors for transplantation will also be eligible to participate in this study.
排除标准
- •Patients undergoing allogeneic HSCT for correction of a primary immunodeficiency disorder (e.g. SCID).
- •Patients with age ≤ 10 years undergoing HSCT with a matched sibling donor. These patients are at very low risk of acute GVHD and do not receive gut decontamination per our institutional standard practice.
- •Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitors, methotrexate or steroids.agents listed above (e.g. abatacept).
- •History of allergic reactions attributed to oral vancomycin or oral polymyxin B.
- •Participants undergoing active therapy for immune-mediated or infectious colitis upon admission for allogeneic HSCT.
- •Participants receiving antibiotic therapy for treatment of a bacterial infection or bacterial prophylaxis upon admission for allogeneic HSCT. Use of any agent (e.g. sulfamethoxazole/trimethoprim) for prophylaxis of Pneumocystis jirovecii pneumonia is permitted. Concurrent use of anti-fungal and anti-viral therapies is also permitted.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
研究组 & 干预措施
Gut Decontamination with vancopoly
- All eligible participants will be randomized to either Arm A: "Gut Decontamination" or Arm B: "No Gut Decontamination".
- Participants assigned to this arm will receive non-absorbable, oral vancomycin-polymyxin B as per our institutional standard practice.
干预措施: Vancomycin-polymyxin B (Drug)
结局指标
主要结局
Gut Microbiome Description
时间窗: 2 Weeks post HSCT
Shannon diversity index (range: 0-6), measured at 2 weeks post stem cell transplant. Shannon diversity is a way to calculate biodiversity in a community, and assumes that all species are represented in a sample and that they are randomly sampled. Shannon Diversity is a measurement sensitive to the loss of rare taxa (34 in the JCI Insight manuscript, Konopinski MK, PeerJ. 2020;8:e9391) and estimates microbial richness (e.g., the number of species) and evenness (e.g., the relative abundance of organisms within a sample). Formula 1: H = -∑\[(pi) \* ln(pi)\], * H: Shannon diversity index (H = 0 indicates that a community has only one species) pi: Proportion of individuals of i-th species in a whole community Formula 2: pi = n / N, * n: individuals of a given type/species * N: total number of individuals in a community
次要结局
- Diarrhea Frequency(Participants were followed 7 days after HSCT.)
- Overall Survival Rate at 12 Months (OS12)(All participants were followed for 1 years after study entry.)
- Incidence of Acute GVHD (Grade 2-4)(Each stool collection time point after neutrophil engraftment until day +100)
- Median Absolute Cell Numbers of T-, B-, NK- and Dendritic Cell Subsets by Flow Cytometry(Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant))
- Relapse Free Rate at 12 Months(Patients were followed for 12 months.)
研究者
Leslie Lehmann, MD
Principal Investigator
Dana-Farber Cancer Institute