Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Event-free survival
研究概览
简要总结
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity 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 7-20% of graft failures in different diseases. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of diseases. In two previously completed trials of addition of either bendamustine and ruxolitinib to conditioning we observed low rates of primary graft failure with both approaches. The study is the direct randomized comparisons of these two approaches with the primary aim of reducing composite events of primary graft failure, relapse and non-relapse mortality. The stratas for the study are Disease Risk Index (DRI) and the age of the haploidentical donor (<35 vs ≥35).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, mixed lineage acute leukemia, lymphoblastic lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, myeloprolipherative neoplasm
- •Malignant disease in hematologic response: <5% of clonal blasts in the bone marrow and no clonal blasts in peripheral blood.
- •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
排除标准
- •Titer of anti-donor anti-HLA antibodies ≥ 5000 at the time of inclusion
- •Moderate or severe cardiac disease: ejection fraction <50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
- •Stroke within 3 months of inclusion, unless related to the underlying malignancy
- •Severe decrease in pulmonary function: FEV1 <50% or DLCO<50% of predicted or respiratory distress or need for oxygen support;
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- •Creatinine clearance < 40 mL/min
- •Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP> 70 mg/L
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <70%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
研究组 & 干预措施
FluBeBu conditioning
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 90 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 +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os.
干预措施: Bendamustine Hydrochloride (Drug)
FluBeRux conditioning
Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -2: ruxolitinib 5 mg tid per os; 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 +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Event-free survival
时间窗: 2 years
Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
次要结局
- Cumulative incidence of primary and secondary graft failure(365 days)
- Incidence of HSCT-associated adverse events (safety and toxicity)(125 days)
- Non-relapse mortality analysis(2 years)
- Incidence of moderate and severe chronic GVHD(2 years)
- Overall survival analysis(2 years)
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence(100 days)
- Relapse cumulative incidence analysis(2 years)
- Cumulative incidence of acute GVHD grade II-IV(125 days)
- GVHD-relapse-free survival analysis(2 years)
研究者
Ivan S Moiseev
Vice-director of RM Gorbacheva Research Institute
St. Petersburg State Pavlov Medical University