Clinical Study of rATG Individualized Administration for Prevention of GVHD and Maintenance of GVL in Haploidentical Hematopoietic Stem Cell Transplantation.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Leukemia-free survival (LFS)
研究概览
简要总结
The purpose of this prospective, open-label, pairing design, single-center study is to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen（10mg/kg）for patients with acute leukemia undergoing a myeloablative conditioning regimen and haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
详细描述
Allogeneic hematopoietic stem-cell transplantation (HSCT) is a potentially curative treatment option for acute leukemia. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has become the main choice for acute leukemia in China. Major difficulties of the procedure include graft-versus-host disease (GVHD), graft failure, and relapse. As an important role of haplo-HSCT, Rabbit anti-thymocyte globulin (rATG), a polyclonal rabbit-derived antibody that depletes lymphocytes, including T cells, was introduced to prevent GVHD and transplant rejection.
The recommended dose of rATG in haplo-HSCT is 10 mg/kg. However, while the traditional weight-based rATG dosing regimen (10mg/kg) reduces the incidence of GVHD, it increases the risk of delayed immune reconstitution, viral reactivation, and relapse in patients. Our previous retrospective study showed that active ATG exposure (area under the curve, AUC)) post-transplantation is associated with immune reconstitution, GVHD, relapse, survival, and viral reactivation in HSCT of acute leukemia patients. Identifying the optimal dose of ATG to achieve the optimal exposure range of active ATG is a pressing clinical issue.
The pharmacokinetics of ATG varies significantly in both pediatric and adult populations, especially the active ATG levels, and clarifying the relationship between the pharmacokinetics of ATG and the prognosis of patient outcomes can help in precise treatment. By constructing a population pharmacokinetic model of ATG, we can provide an individualized optimal dose of ATG based on factors prior to transplantation. ATG individualized administration may improve the survival and quality of life of patients undergoing haplo-HSCT. A prospective pairing design trial is required to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen (10mg/kg) for patients with acute leukemia undergoing haplo-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients were diagnosed with acute leukemia.
- •All patients should have the indication of Haploidentical hematopoietic stem cell transplant and receive the myeloablative conditioning regimen.
- •All patients should sign an informed consent document indicating that they understand the purpose of and procedures required for the study and be willing to participate in the study.
排除标准
- •Patients with any conditions not suitable for the trial (investigators' decision).
研究组 & 干预措施
Individual dose of ATG
The total individual ATG dose was calculated based on population pharmacokinetic modeling. ATG was intravenously infused every day from day -5 to day -2.
干预措施: Individual ATG (Drug)
ATG 10mg/kg
The total ATG dose was 10mg/kg. ATG was intravenously infused every day from day -5 to day -2.
干预措施: ATG (Drug)
结局指标
主要结局
Leukemia-free survival (LFS)
时间窗: 1 years after transplantation
Leukemia-free survival (LFS) is defined as the time from enrollment to relapse of primary disease or death from any cause, whichever occurred first.
Cumulative incidences of aGVHD
时间窗: 100 days after transplantation
The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.
CD4+ immune reconstitution
时间窗: 3 months after transplantation
CD4+ T-cells \>0·05 × 10⁹/L twice within 3 months after transplantation
次要结局
- Cumulative incidences of cGVHD(1 years after transplantation)
- Cumulative incidences of EBV reactivation(1 years after transplantation)
- Neutrophil engraftment(1 month after transplantation)
- Platelet engraftment(1 month after transplantation)
- Overall survival (OS)(1 years after transplantation)
- Relapse-related mortality (RRM)(1 years after transplantation)
- Cumulative incidence of CMV reactivation(1 years after transplantation)
- GVHD-free and relapse-free survival (GRFS)(1 years after transplantation)
- Non-relapse mortality (NRM)(1 years after transplantation)