Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)
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
- Event-free survival analysis [ Time Frame: 1 year ]
研究概览
简要总结
Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with indication for allogeneic hematopoietic stem cell transplantation
- •Patients with 5-10/10 HLA-matched related or unrelated 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
- •Diagnosis:
- •Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms
- •Salvage hematopoietic stem cell transplantation defined as:
- •Acute myeloid leukemia: >5% of clonal blasts despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: >10% of blasts despite previous therapy with -7 or complex karyotype, or p53 mutation Chronic myeloid leukemia: blast crisis or acceleration phase despite at least 3 previous lines of TKIs Myeloprolipherative neoplasms : high tumor burden despite previous therapy, including >20 000 WBC/ ul or splenomegaly >15 cm
- •No severe concurrent illness
排除标准
- •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
PTBCy graft-versus-host disease prophylaxis
Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Bendamustine Hydrochloride (Drug)
PTBCy graft-versus-host disease prophylaxis
Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration
干预措施: Cyclophosphamid (Drug)
结局指标
主要结局
Event-free survival analysis [ Time Frame: 1 year ]
时间窗: 1 year
Measure: Kaplan-Meier estimate of death or relapse, or graft failure
次要结局
- Incidence of HSCT-associated adverse events (safety and toxicity)(100 days)
- Non-relapse mortality analysis(1 year)
- Incidence of moderate and severe chronic GVHD(1 year)
- Relapse rate analysis(1 year)
- - Incidence of Cytokine release syndrome(100 days)
- Incidence of acute GVHD grade II-IV(125 days)
- Overall survival analysis(1 year)
研究者
Ivan S Moiseev
Vice-director for science RM Gorbacheva Institute
St. Petersburg State Pavlov Medical University