A Prospective, Single-Arm Clinical Study of Anti-thymocyte Globulin-based Conditioning Regimen Combined With Post-Transplantation Cyclophosphamide for GVHD Prevention in Allogeneic HSCT After PD-1 Blockade
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 22
- 主要终点
- acute graft-versus-host disease
研究概览
简要总结
The aim of this study is to evaluate the efficacy and safety of anti-thymocyte globulin combined with PTCy (post-HSCT cyclophosphamide, PTCy) in preventing graft-versus-host disease (GVHD) in allo-HSCT patients after anti-PD-1(anti-programmed cell death protein 1) antibody treatment. In this study, patients with hematological malignancies who needed to receive allo-HSCT after PD-1 antibody treatment were selected as the research subjects. Fludarabine and Busulfan was used as the conditioning regimen, and the dose of ATG (anti-thymocyte globulin, ATG) combined with PTCy was used as the GVHD prevention regimen. The aim of this study is to reduce the incidence of Regimen-Related Toxicity and GVHD without affecting engraftment and relapse, thereby reducing non-relapse mortality and further improving the survival of patients.
详细描述
ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and unrelated donor-HSCT. Reduced-dose PTCy regimen: two doses of 14.5 mg/kg Cy were given on days +3 and +4 post-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) age ≥ 18 years old, regardless of gender;
- •(2) patients with hematological malignancies (including lymphoma, leukemia, myelodysplastic syndrome, etc.) who had received at least one course of PD-1 antibody treatment;
- •(3) patients with indications for allo-HSCT, available donors (including matched sibling donors, haploidentical donors and unrelated donors), and no contraindications for transplantation;
- •(4) patients suitable for conventional Bu/Flu conditioning regimen;
- •(5) no serious heart, liver, kidney, lung and other important organ diseases;
- •(6) Eastern Cooperative Oncology Group (ECOG) performance status score 0-2;
- •(7) Hematopoietic stem cell transplantation comorbidity index (HCT-CI) score was 0-3;
- •(8) expected survival time of at least 12 weeks;
- •(9) women who are not pregnant or breastfeeding;
- •(10) voluntary participation in clinical research; They or their legal guardians were fully aware of the study and signed informed consent. Willing to follow and complete all trial procedures;
排除标准
- •(1) pregnant or lactating women;
- •(2) other serious conditions that may limit enrollment (e.g., advanced infection, etc.);
- •(3) unable to understand and follow the study protocol or sign the informed consent form.
研究组 & 干预措施
Combination of PTCy and ATG for GVHD prophylaxis
ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and unrelated donor-HSCT. Reduced-dose PTCy (two doses of 14.5 mg/kg Cy was given on days +3 and +4 post-HSCT) was used of GVHD prophylaxis.
干预措施: Cyclophosphamid (Drug)
结局指标
主要结局
acute graft-versus-host disease
时间窗: 100 days
Acute graft-versus-host disease severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC). Higher grades mean a worse outcome.
次要结局
- cumulative incidence of relapse(1-year)
- recurrence free survival(1-year)
- non-relapse mortality(1-year)
- overall survival(1-year)
- chronic graft-versus-host disease(1-year)
- GVHD-free/ relapse-free survival(1-year)
- PD-L1 expression in acute myeloid leukemia bone marrow cells(Up to 1 year post-treatment)