The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- neutrophil recovery day
研究概览
简要总结
Aim: To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving immunosuppressive therapy (IST).
Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group
Treatment:
IST group: ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A (CSA) Cord blood transfusion group: In addition to the same dose and course of ATG and CSA , one unit of cord blood having no more than 2 HLA-A, B or DRB1 mismatches is transfused 24h after last dose of ATG administration.
详细描述
Eligible patients should be under 60 years old with confirmed SAA, without HLA matched siblings and previous ATG treatment history. Patients will be excluded if they present any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al or severely allergic to biologic products.
To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving IST therapy, 120 eligible patients will be randomized to two groups, the IST group and the cord blood transfusion group. Patients in the IST group receive standard IST which including ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A（CSA ) started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml. While patients in the cord blood transfusion group receive the same dose and course of ATG and CSA as the control group and one unit of cord blood having no more than 2 HLA-A, B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
The neutrophil recovery day is defined as the first day of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×109/L, without G-CSF adminstration. Platelet recovery day is defined to have occurred on the first of 7 consecutive days with a blood platelet count (BPC) of >20×109/L, without transfusion support. Response (CR, PR or NR) is evaluated on 3, 4, 6,9, 12, 18 and 24months after treatment.
The primary end point is the neutrophil recovery day and second end points are response rate (CR+PR), treatment related mortality, disease free survival and overall survival.
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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
- — 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1．Diagnosis of AA confirmed by bone marrow aspirate and biopsy, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria were excluded. To confirm severe AA, the patient must fulfill at least two of the criteria: i) ANC<0.5×109/L,ii)PLT<20×109/L and iii) Ret<20×109/L ,in addition, ANC<0.5×109/L must be included.
- •Under 60 years old, male or female.
- •No HLA matched siblings.
- •No previous ATG treatment history.
- •Performance status score no more than 2 (ECOG criteria).
- •6．Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal) Serum creatinine and BUN <1.25×ULN.
- •Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
- •8．Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- •Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.
排除标准
- •Presence of any condition inappropriate for HSCT.
- •Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
- •3．Severely allergic to biologic products.
- •4．Pregnancy or breastfeeding.
- •5．Current treatment on another clinical trail.
- •6．Any other condition the investigator judged the patient inappropriate for entry into this study.
研究组 & 干预措施
cord blood and IST group
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
干预措施: Cord blood (Procedure)
cord blood and IST group
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
干预措施: Thymoglobulin (Drug)
cord blood and IST group
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
干预措施: Cyclosporine Oral Product (Drug)
IST group
Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.
干预措施: Thymoglobulin (Drug)
IST group
Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.
干预措施: Cyclosporine Oral Product (Drug)
结局指标
主要结局
neutrophil recovery day
时间窗: 5 days to 365 days
the first day of 3 consecutive days when the absolute neutrophil count (ANC) reaches 0.5×10\^9/L, without G-CSF administration . The day of first dose of ATG administration is record as day 0.
次要结局
- overall response rate(3 months to 24 months)
- overall survival(24month)
研究者
Chun Wang
director, department of hematology
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine