Safety and Efficacy Study of Busulfan/FLAG Conditioning Regimen in Patients With Relapsed/Refractory Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 主要终点
- Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria
研究概览
简要总结
The purpose of this study is to determine the safety and efficacy of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) Conditioning Regimen in Patients with Relapsed/refractory Acute Leukemia undergoing allogeneic peripheral blood stem cell transplantation.
详细描述
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only way to cure relapsed/refractory acute leukemia. Busulfan/Cyclophosphamide (BuCy, Cytarabine, Busulfan, Cyclophosphamide) has been a classical conditioning regimen for allo-SCT. Substitution of Cyclophosphamide in the BuCy regimen with Fludarabine (BuF) resulted in reduced toxicity and similar efficacy. FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) is a chemotherapy regimen that has been proved to be effective for relapsed/refractory acute leukemia as salvage therapy. To reduce the relapse and improve the survival of those patients with relapsed/refractory acute leukemia who receive allo-SCT, the novel conditioning regimen consisting of Busulfan/FLAG was developed. The combination of Bu and FLAG without interval shortens the duration of conditioning and the pneutropenic period of the patient compared with successive administration of FLAG followed with BuF. In addition, regarding the established safety and efficacy of BuF and FLAG, it is reasonable to expect similar safety and enhanced antileukemic efficacy for Bu/FLAG compared with BuF. In this study, the safety and efficacy of this regimen in patients with relapsed/refractory acute leukemia undergoing allogeneic peripheral blood stem cell transplantation was investigated.
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
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •relapsed/refractory acute leukemia regardless of cytogenetics
- •All patients should aged 12 to 65 years
- •Have matched sibling donors, ≥8/10 HLA(human leukocyte antigen) matched unrelated donors or haploidentical donors
- •Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases
排除标准
- •Patients aged less than 12 years old
- •Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases
- •Acute myeloid leukemia patients with t (15;17)
研究组 & 干预措施
Busulfan/FLAG conditioning regimen
All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor).
The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days
-7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).
干预措施: Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd) (Drug)
Busulfan/FLAG conditioning regimen
All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor).
The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days
-7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).
干预措施: Cytarabine(Actavis Italy S.p.A) (Drug)
Busulfan/FLAG conditioning regimen
All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor).
The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days
-7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).
干预措施: Fludarabine (Bayer) (Drug)
Busulfan/FLAG conditioning regimen
All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor).
The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days
-7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).
干预措施: granulocyte colony-stimulating factor (KirinKunpeng) (Drug)
Busulfan/FLAG conditioning regimen
All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor).
The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days
-7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).
干预措施: rabbit ATG（Sanofi/Genzyme） (Drug)
结局指标
主要结局
Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria
时间窗: two years
次要结局
- Rate of Complete Remission as assessed by NCCN (National Comprehensive Cancer Network )criteria(30 days)
- DFS(disease-free survival )(two years)
- TRM(treatment-related mortality )(two years)
- Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)(three months)
- Number of participants with Regimen-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03(30 days)
研究者
Daihong Liu
Head of Hematology departemnt in Chinese PLA General Hospital
Chinese PLA General Hospital