Safety and Efficacy of Cyclophosphamide and Ruxolitinib for Graft-versus-host-disease Prophylaxis After Hematopoietic Stem Cell Transplantation With Thymoglobulin Serotherapy in Conditioning Regimen in Patients With Inborn Errors of Immunity
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Event-free survival
研究概览
简要总结
The aim of the current study is to evaluate the efficacy of combined regimen of GVHD prophylaxis with thymoglobulin in conditioning regimen and PTCY with ruxolitinib used after HSCT in patients with inborn errors of immunity (IEI)
详细描述
Hematopoietic stem cell transplantation (HSCT) is widely used in inborn errors of immunity (IEI), and risks of graft-versus-host disease (GVHD) remain high. Use of post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis revolutionized the outcomes of HSCT from mismatched related donor (MMRD). Use of ruxolitinib for GVHD prophylaxis demonstrates promising results in adult patients. Another well-known option for GVHD prevention is antithymocyte globulin. To evaluate the efficacy of combination of thymoglobulin with PTCY and ruxolitinib for GVHD prophylaxis, conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, and thiotepa 10 mg/kg or melphalan 140 mg/m2 and GVHD prophylaxis regimen containing cyclophosphamide 50 mg/kg for MMRD, 25 mg/kg for matched unrelated and related donors at days +3, 4 post-HSCT and ruxolitinib at dose 7 mg/m2 from day +5 after HSCT will be used in patients with IEI.
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
- 0 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 0 months and < 21 years
- •Patients diagnosed with NBS eligible for an allogeneic HSCT
- •Signed written informed consent signed by a parent or legal guardian
排除标准
- •Concomitant severe somatic disease associated with an additional risk of severe complications
研究组 & 干预措施
intervention/treatment
Conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, thymoglobulin 5 mg/kg and thiotepa 10 mg/kg or melphalan 140 mg/m2
GVHD prophylaxis regimen for matched unrelated (MUD) and matched related donors (MRD):
Cyclophosphamide (PTCY) 25 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
GVHD prophylaxis regimen for mismatched related donor (MMRD):
Cyclophosphamide (PTCY) 50 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
干预措施: Cyclophosphamide (Drug)
intervention/treatment
Conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, thymoglobulin 5 mg/kg and thiotepa 10 mg/kg or melphalan 140 mg/m2
GVHD prophylaxis regimen for matched unrelated (MUD) and matched related donors (MRD):
Cyclophosphamide (PTCY) 25 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
GVHD prophylaxis regimen for mismatched related donor (MMRD):
Cyclophosphamide (PTCY) 50 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Event-free survival
时间窗: 1 year after HSCT
Events: graft failure, death
次要结局
- Cumulative incidence of chronic graft versus host disease(1 year after HSCT)
- Incidence of early organ toxicity(100 days)
- Overall survival(1 year after HSCT)
- Cumulative incidence of engraftment(100 days)
- Cumulative incidence of graft failure(1 year after HSCT)
- Cumulative incidence of viral infections(1 year after HSCT)
- Cumulative incidence of acute graft versus host disease(1 year after HSCT)
- Cumulative incidence of transplant related mortality(1 year after HSCT)
- Investigation of the concentration of ruxolitinib in the blood To investigate the pharmacokinetics of ruxolitinib(1 month after HSCT)