Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
研究概览
简要总结
To determine whether treatment with ustekinumab will alter the ratio of T Regulatory Cell (Treg)/total cluster of differentiation 4 (CD4)+ cells in peripheral blood at day 30 post-hematopoietic cell transplantation (HCT).
详细描述
This is a comparative study to assess the biologic and clinical activity of the agent ustekinumab when given in concert with our established regimen of SIR/TAC. Patients will be randomly assigned between the standard regimen of tacrolimus/sirolimus (TAC/SIR + placebo) vs. the investigational regimen of tacrolimus/sirolimus/ustekinumab (TAC/SIR/U) in a 1:1 scheme.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hematologic disorder requiring allogeneic hematopoietic cell transplantation
- •Adequate vital organ function:
- •Left ventricular ejection fraction (LVEF) >/= 45% by multigated acquisition (MUGA) scan
- •FEV1, FVC, and diffusing lung capacity oxygenation (DLCO) >/= 50% of predicted values on pulmonary function tests
- •Transaminases (AST, ALT) < 3 times upper limit of normal values
- •Creatinine clearance >/= 50 cc/min.
- •Performance status: Karnofsky Performance Status Score >/= 60%.
排除标准
- •Active infection not controlled with appropriate antimicrobial therapy
- •HIV, hepatitis B, or hepatitis C infection
- •Sorror's co-morbidity factors with total score > 3
- •Important modification to co-morbidity index calculation: DLCO will not be included in assessment of pulmonary risk, excepting those with DLCO < 50%, who will merit a score of 3 and thereby be excluded from the trial.
- •Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- •Cyclophosphamide as part of the conditioning regimens
研究组 & 干预措施
Ustekinumab
Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Ustekinumab (Drug)
Ustekinumab
Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Tacrolimus (TAC) (Drug)
Ustekinumab
Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Sirolimus (Drug)
Placebo
Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Placebo (Drug)
Placebo
Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Tacrolimus (TAC) (Drug)
Placebo
Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.
干预措施: Sirolimus (Drug)
结局指标
主要结局
T Regulatory Cell (Treg)/Total Cluster of Differentiation 4 (CD4)+ Ratio
时间窗: 30 days post transplant
Median Blood Treg/Total CD4+ Ratio at day 30 following hematopoietic cell transplantation (HCT). Comparison between study arms: Ustekinumab vs. Placebo. From NCI Dictionary: "T reg" - A type of immune cell that blocks the actions of some other types of lymphocytes, to keep the immune system from becoming over-active. T regs are being studied in the treatment of cancer. A T reg is a type of white blood cell and a type of lymphocyte. Also called regulatory T cell, suppressor T cell, and T-regulatory cell.
次要结局
- Incidence of Acute Graft vs. Host Disease (AGVHD)(100 days post transplant)