Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia Patients Undergoing HSCT
试验速览
- 阶段
- 2 期
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- 1 year cumulative incidence of relapse
研究概览
简要总结
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. We reported previously that patients with relapse or refractory AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastic syndrome. It was reported that the combination of decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory AL patients.
详细描述
Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.
BM(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 years after transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients with relapsed acute leukemia
- •patients with acute leukemia in the third（or more）complete remission (CR3) status
排除标准
- •pregnancy women
- •uncontrolled severe infection
研究组 & 干预措施
Decitabine plus mBU/CY for HLA-mismatched HSCT
Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT
Details:
The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
干预措施: Decitabine (Drug)
Decitabine plus mBU/CY for HLA-mismatched HSCT
Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT
Details:
The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
干预措施: mBU/CY and ATG (Drug)
Decitabine plus mBU/CY for matched sibling transplant
Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant.
Details:
In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3.
干预措施: Decitabine (Drug)
Decitabine plus mBU/CY for matched sibling transplant
Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant.
Details:
In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3.
干预措施: mBU/CY (Drug)
结局指标
主要结局
1 year cumulative incidence of relapse
时间窗: 1 year post allo-HSCT
The cumulative incidence of relapse at 1 year post allo-HSCT
2 year cumulative incidence of relapse
时间窗: 2 years post allo-HSCT
The cumulative incidence of relapse at 2 years post allo-HSCT
次要结局
- Non-relapse mortality(1 year post allo-HSCT)
- engraftment(100 days post allo-HSCT)
- Acute graft versus host disease(100 days post allo-HSCT)
- 1 year overall survival(1 year post allo-HSCT)
- 5 years overall survival(5 years post allo-HSCT] 1 year leukemia free survival)
- 1 year leukemia free survival(1 year post allo-HSCT)
- 5 years leukemia free survival(5 years post allo-HSCT)
- Chronic graft versus host disease(1 years post allo-HSCT)
研究者
Xiaojun Huang,MD
Director of the Hematology Department
Peking University People's Hospital