A Randomized Trial of Thymoglobulin to Prevent Chronic Graft Versus Host Disease in Patients Undergoing Hematopoietic Progenitor Cell Transplantation (HPCT) From Unrelated Donors
试验速览
- 阶段
- 3 期
- 入组人数
- 198
- 试验地点
- 20
- 主要终点
- Freedom from Chronic GVHD
研究概览
简要总结
This is a randomized trial for patients undergoing hematopoietic progenitor cell transplantation (HPCT) from an unrelated donor. Approximately 50% of the patients enrolled will receive Thymoglobulin® as part of the preparative regimen prior to HPCT. The other 50% of the patients enrolled will receive a standard preparative regimen. Thymoglobulin is known to suppress the types of cells that can cause a transplant complication known as "chronic graft versus host disease (cGVHD)". The goal of this trial is to find out if adding Thymoglobulin to the preparative regimen will result in a decrease in cGVHD.
详细描述
This study is a non-blinded, randomized, multicentre trial testing the effect of Thymoglobulin® vs. placebo on the primary outcome of cGVHD. Subjects will be children and adults having unrelated donor transplants.
Intervention: Infusion of Thymoglobulin® on three days prior to the transplant.
Hypothesis
The hypothesis is that the use of Thymoglobulin® in the experimental group will result in an absolute 20% increase in the number of patients free of cGVHD at 12 months, the time of peak incidence, from 20% in the control group to 40% in the experimental group.
Outcome Measures: The Primary Outcome Measure is freedom from cGVHD at 12 months from transplantation, defined as withdrawal of all systemic immunosuppressive agents and without resumption up to 12 months (a binary end-point, yes/no). Secondary outcome measures: Quality of Life, overall incidence of cGVHD (including untreated cases and resolved cases), the incidence of "extensive" cGVHD, time to non-relapse mortality, time to all-cause mortality, time to relapse of leukemia, graft rejection or failure (Yes vs. No), serious infection (Yes vs. No), CMV activation (Yes vs. No), organ-specific grading of chronic graft versus host disease, resumption of immunosuppressive agents after 12 months (Yes vs. No), doses of immunosuppressive drugs still required at 12 months, and incidence of acute graft versus host disease.
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 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The recipient has a hematologic malignancy
- •The recipient will receive one of the specified preparative regimens
- •The recipient will receive either a bone marrow ("HPC, Marrow") or blood progenitor cell ("HPC, Apheresis") graft
- •The recipient has an unrelated donor who with high resolution typing is either fully MHC matched at HLA-A, B, C and DRB1 with the recipient or is 1-antigen or 1-allele mismatched at A, B, C or DRB1 loci The recipient meets the transplant centre's criteria for unrelated donor allogeneic transplantation , either myeloablative or non-myeloablative (syn. RIC).
- •The recipient has good performance status (Karnofsky ≥60%)
- •Recipient has given signed informed consent For the questionnaire component only, be able to complete the questionnaires in English or with a validated translation (as posted on the project website)
排除标准
- •The recipient is HIV antibody positive
- •The recipient has a hypersensitivity to rabbit proteins or Thymoglobulin pharmaceutical excipients, glycine or mannitol
- •The recipient has active or chronic infection (i.e. infection requiring oral or IV therapy)
- •The recipient (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrollment
- •The recipient (if female and of childbearing potential) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant
- •The recipient (if male and fertile) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant
- •For the questionnaire component only, the recipient is unable to participate due to cognitive, linguistic or emotional difficulties (i.e. the recipient can participate in the main study but will be excluded from the questionnaire component
结局指标
主要结局
Freedom from Chronic GVHD
时间窗: 12 months post transplant
"Freedom from Chronic GVHD" is defined as withdrawal of all systemic immunosuppressive agents and without resumption up to 12 months (a binary endpoint, yes/no)
次要结局
- Quality of Life(Measured at Screening, Month 6, 12 and 24)