Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- - Incidence of primary and secondary graft failure
研究概览
简要总结
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 10-20% of graft failures. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of disease. Furthermore combination of fludarabine and bendamustine was sufficient to facilitate engraftment in patients with chronic lymphocytic leukemia and lymphomas. The aim of the study is to evaluate whether addition of bendamustine to fladarabine and busulfan conditioning reduces the risk of primary graft failure after haploidentical allograft.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
- •Patients with 5-9/10 HLA-matched related donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB
- •Peripheral blood stem cells or bone marrow as a graft source
- •No second malignancies requiring treatment
- •No severe concurrent illness
排除标准
- •Titer of anti-HLA antibodies ≥ 5000 at the time of inclusion
- •Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- •Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- •Respiratory distress >grade I
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- •Creatinine clearance < 60 mL/min
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <30%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
研究组 & 干预措施
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Fludarabine (Drug)
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Bendamustine Hydrochloride (Drug)
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Busulfan (Drug)
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Cyclophosphamide (Drug)
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Mycophenolate Mofetil (Drug)
FluBuBe
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Tacrolimus 5Mg Cap (Drug)
结局指标
主要结局
- Incidence of primary and secondary graft failure
时间窗: 100 days
Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism
次要结局
- - Incidence of HSCT-associated adverse events (safety and toxicity)(125 days)
- - Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence([ Time Frame: 100 days ] [ Designated as safety issue: Yes ])
- - Incidence of acute GVHD grade II-IV(125 days)
- - Incidence of moderate and severe chronic GVHD(365 days)
- - Non-relapse mortality analysis(2 years)
- - Overall survival analysis(2 years)
- - Event-free survival analysis(2 years)
- - Relapse rate analysis(2 years)
研究者
Ivan S Moiseev
Vice-pdirector for science RM Gorbacheva Institute
St. Petersburg State Pavlov Medical University