Pharmacodynamics, Pharmacogenomics, and Preliminary Safety and Efficacy of Alemtuzumab Induction and Tacrolimus in Pediatric Intestinal Transplantation (IND # 100496)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 主要终点
- Incidence of Post Transplant Lymphoproliferative Disorder (PTLD)
研究概览
简要总结
This open-label clinical trial will evaluate the safety and efficacy of Alemtuzumab (Campath, Bayer Corp., Pittsburgh) in children (0-17) and adults (18-25) receiving intestinal transplant. Seventy-five subjects receiving primary or repeat intestine transplantation will be enrolled. Primary endpoints include the incidence and severity of biopsy-proven acute cellular rejection, the incidence of freedom from steroids at 5 years, and the incidence of subjects with steroid-free Tacrolimus at whole blood concentrations < 10 ng/ml. Secondary endpoints include a) incidence and severity of opportunistic infections (CMV and EBV), post-transplant lymphoproliferative disorder (PTLD), and chronic rejection b) use of non-immunosuppressive co-medications, c) time to repopulation of all lymphocyte subsets, d) longitudinal characterization of donor-specific alloreactivity in mixed lymphocyte responses (MLR), to identify the time at which it decreases to a level less than third-party-specific alloreactivity e) longitudinal expression (mRNA) of genes, to identify rejection- and non-rejection-specific genes and f) characterization of whole genome mutations, which show differences in parent-to-child transmission between rejectors and non-rejectors. This will identify rejection- and non-rejection-specific genes bearing genetic variants, which might impact on gene function, and complement candidate gene identification efforts based on SNP transmission.
详细描述
Intraoperatively, it is our impression that Alemtuzumab may predispose to mild coagulopathy. Therefore, we have elected to administer steroids, and withhold Alemtuzumab in the operating room for all small bowel transplant recipients.
- Premedication with acetaminophen 10 mg/kg orally + diphenhydramine 1 mg/kg intravenously + methylprednisolone 2 mg/kg, intravenously will occur 30 minutes before Alemtuzumab administration.
- Steroids up to 10 mg/kg as bolus will be administered intravenously in the operating room prior to reperfusion of the allograft followed by decreasing amounts of low-dose steroids post-transplant.
Day 1 post-transplant: up to 5 mg/kg can be given Day 2 post-transplant: up to 4 mg/kg can be given Day 3 post-transplant: up to 3 mg/kg can be given Day 4 post-transplant: up to 2 mg/kg can be given Day 5 post-transplant: up to 1 mg/kg can be given
Maintenance steroids are tapered thereafter by switching to equivalent amounts of oral prednisone, as soon as ileus results and oral intake intake is possible. By the end of the first month, all patients receive no more than 2.5-5 mg/day of prednisone. This amount is exceeded only if rejection occurs. Long-term prednisone usage may be elected in patients re-transplanted for chronic rejection. 3. A single dose of Alemtuzumab 0.4-0.5 mg/kg will be given intravenously slowly post-operatively. Total dose will not exceed 30 mg.
Procedures:
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
- 年龄范围
- 4 Months 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 0-25 years
- •male and female
- •Primary intestine transplantation, repeat intestine transplantation, and intestine transplantation in the setting of a previous or simultaneous liver transplantation
排除标准
- •documented non-compliance
- •known hypersensitivity to egg protein
- •pregnancy
- •malignancy
- •hepatitis C and B defined as anti-HCV antibody positive, and anti-Hepatitis B surface antigen or Hepatitis B core antibody positive or HBV DNA positive.
研究组 & 干预措施
Alemtuzumab induction
Intestine transplant recipients who receive induction with alemtuzumab prior to transplantation.
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Incidence of Post Transplant Lymphoproliferative Disorder (PTLD)
时间窗: 5 Year
Asses safety of Alemtuzumab in combination with Tacrolimus and steroids in twenty-three pediatric intestine allograft recipients by calculating the rate in which PTLD occurred amongst the study population.
次要结局
- Incidence of Biopsy-proven Acute Cellular Rejection(1 Year)
- Incidence of Patients in Whom Steroids Are Not Used(5 year)
- Incidence of Patients in Whom Tacrolimus Whole Blood Concentration Less Than 10 ng/ml Are Being Used at 1-year Follow-up.(1 year)
研究者
Rakesh Sindhi
Professor of Surgery
University of Pittsburgh