Randomized Study of Atorvastatin Prophylaxis as a Supplement to Standard of Care Prophylaxis to Prevent Chronic Graft Versus Host Disease Allogeneic Stem Cell Transplantation From Matched Unrelated Donors
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- The primary objective is to determine the cumulative incidence of chronic GVHD at one year after stem cell transplantation and treatment with atorvastatin
研究概览
简要总结
Chronic Graft Versus Host Disease (GVHD) is one of the most challenging complications in long term survivors of allogeneic stem cell transplantation. As the number of allogeneic stem cell transplantations rises annually, the incidence of chronic GVHD rates have also increased due to a variety of factors including but not limited to increasing use of peripheral blood stem cell (PBSC) grafts, increasing age of both donors and recipients, and increased use of matched unrelated donors. One study showed much lower than traditional acute GHVD rate and chronic GHVD which is similar with historical rates when atorvastatin was administered prophylactically to both the donors as well as recipients of matched related allogeneic stem cell transplantation, lead to the interest in further examining the role of Atorvastatin in relation to the development of GVHD. The investigator hypothesize that the administration of atorvastatin in recipients of matched unrelated allogeneic stem cell transplantation, a group with known higher incidence of chronic GHVD, would be a safe and effective method to reduce the incidence of chronic GVHD. Matched related allogeneic stem cell transplantation recipients will not be included in this study due to their significantly lower GVHD rates. The definition and monitoring of our primary endpoint of GVHD is well established in clinical trials in allogeneic stem cell transplantations and the investiagor will utilize the National Institutes of Health (NIH) Staging System for the diagnosis and severity assessment of chronic GVHD as well the recommendations from the NIH Consensus Conference for the conduct of clinical trials in chronic GVHD.
Several secondary endpoints will be examined as defined below and include standard complementary data in the examination of clinical trials in chronic GVHD again as laid out by the NIH Consensus Conference for conduct of clinical trials in chronic GHVD.
详细描述
This is a randomized, open label phase III trial in patients with Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, and Myelodysplastic Syndrome undergoing matched unrelated donor transplant.
Patients randomized to the treatment arm (atorvastatin):
The prophylaxis atorvastatin treatment (taken by mouth) for GVHD will start at 14 days prior to transplant and continue until 365 days post-transplant or until development of significant adverse events or desire of the primary treating physician to stop the administration.
The patients will also receive our institution's standard graft versus host disease prophylactic regimen which consists of two drugs. It has been shown that immunosuppression with two drugs is better than a single agent thus our institution utilizes a combination of Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate will be administered intravenously (IV) post-transplant on Days 1, 3 and 6. Tacrolimus will be administered 2 days prior to transplant and continue approximately 180 days post-transplant. Tacrolimus will be administered IV until patient can take it by mouth.
Patients randomized to standard of care:
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A: Atorvastatin
The preventative atorvastatin treatment 40mg daily by mouth for GVHD will start at 14 days prior to transplant & continue until 365 days post-transplant or if significant adverse events occur. Patients will also receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.
干预措施: Atorvastatin (Drug)
Arm A: Atorvastatin
The preventative atorvastatin treatment 40mg daily by mouth for GVHD will start at 14 days prior to transplant & continue until 365 days post-transplant or if significant adverse events occur. Patients will also receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.
干预措施: Methotrexate (Drug)
Arm A: Atorvastatin
The preventative atorvastatin treatment 40mg daily by mouth for GVHD will start at 14 days prior to transplant & continue until 365 days post-transplant or if significant adverse events occur. Patients will also receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.
干预措施: Tacrolimus (Drug)
Arm B: Standard of Care
Patients will receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.
干预措施: Methotrexate (Drug)
Arm B: Standard of Care
Patients will receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
The primary objective is to determine the cumulative incidence of chronic GVHD at one year after stem cell transplantation and treatment with atorvastatin
时间窗: 2 years
National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form
次要结局
- To determine rate of disease relapse(2 years)
- To determine the cumulative incidence of grade 3 to 4 acute GVHD(100 days)
- To determine non-relapse mortality (NRM)(2 years)
- To determine progression-free survival (PFS)(2 years)
- To determine overall survival (OS)(2 years)
- Determine the frequency and severity of chronic GVHD(2 years)
- Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 4(30 days of the last dose of protocol treatment)
研究者
Patrick Stiff
Professor
Loyola University