Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- The total response rate
研究概览
简要总结
To assess whether ATG Combined With Cyclophosphamide and cord blood infusion can accelerate hematopoietic reconstruction in severe aplastic anemia patients and improve clinical curative effect and safety
详细描述
Aplastic Anemia( AA), is a set of bone marrow hematopoietic dysfunction caused by a variety of causes, with hyperplasia of bone marrow hematopoietic cells to reduce whole blood cells and peripheral blood at the characteristics of clinical main performance for anemia, bleeding and infection. According to the severity of the bone marrow failure and the progress of the clinical course ,it is divided into Severe Aplastic Anemia (SAA) and the Non - Severe Aplastic Anemia (NSAA).Severe Aplastic Anemia can be divided into two categories: Very Severe Aplastic Anemia (VSAA) and Severe Aplastic Anemia (SAA), with the characteristics of rapid progress, refractory, poor prognosis, high mortality .The natural course is six months or so, and most patients die in a year . Hematopoietic stem cell transplantation and immunosuppressive therapy are two main treatment . The former is by far the only possible cure. It is recommended as first-line treatments, if patients have a matched sibling donor. The recommended age limit is 40 years old. But for those who have no sibling donor or patients older than 40 years old, it is recommend the immunosuppressive therapy.
The investigators have already summarized the effectiveness of rabbit antithymocyte immunoglobulin (ATG), cyclophosphamide (Cy) and cyclosporine, A (CsA) and the combination of the umbilical cord blood infusion for SAA/VSAA patients without suitable donor, with short duration, without long-term immunosuppressive therapy history. The total effectiveness rates has improved to 88%, with shorter immunosuppressive maintaining therapy , rapid hematopoietic reconstruction, fewer complications. The aim of this study is to further explore whether this solution can accelerate hematopoietic reconstruction of SAA/VSAA patients and its clinical curative effect and security. This study scheme has been approved by the Jinan military region general hospital medical ethics committee.
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
- 1 Year 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ,under the age of
- •Diagnosis of SAA and VSAA in accordance with the <aplastic anemia, diagnosis and treatment expert consensus> Camitta standard (see appendix 1).
- •Confirmed of heavy and very heavy aplastic anemia within 6 months.
- •No obvious abnormal liver and kidney function: ALT, AST,≤2.5 times the upper limit of normal , serum Creatinine and BUN ≤1.25 times the upper limit of normal
- •Clear understanding, voluntary to participate in the study, and signed informed consent document by the patient or the legal guardian
- •Willingness and ability to comly with the treatment plan, follow-up and laboratory tests as required
排除标准
- •Congenital aplastic anemia
- •Pregnancy or breastfeeding
- •Participated in other clinical trials within three months
- •Presence of Any fatal disease, including respiratory failure, heart failure, liver or kidney failure, et al
- •Aplastic anemia caused by the treatment of other malignant tumor treatment
- •With severe mental illness
- •With other malignant tumor
- •Severe infection or the infection difficult to be controlled
- •Received ATG or cyclosporine A within six months
- •Severely allergic to biological agents
- •Any other situation judged by the investigator that the patients inappropriate for entry into this study
研究组 & 干预措施
ATG, Cy and cord blood transfusion group
ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
Intervention:
Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
干预措施: Rabbit ATG, (Genzyme) (Drug)
ATG, Cy and cord blood transfusion group
ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
Intervention:
Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
干预措施: Cy (Drug)
ATG, Cy and cord blood transfusion group
ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
Intervention:
Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
干预措施: CsA (Drug)
ATG, Cy and cord blood transfusion group
ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
Intervention:
Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
干预措施: Cord blood (Biological)
ATG and CSA group
ATG 3mg/kg/d for 5 days CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus CSA
干预措施: Rabbit ATG, (Genzyme) (Drug)
ATG and CSA group
ATG 3mg/kg/d for 5 days CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus CSA
干预措施: CsA (Drug)
结局指标
主要结局
The total response rate
时间窗: Every 3 months to 24 months
Response rate is the ratio of CR and PR patients to all evaluated patients at the time point. CR,PR,NR and relapse is evaluated according to the guidelines for the diagnosis and management of adult aplastic anaemia from British Committee for Standards in Haematology (BCSH)
次要结局
- Infection rates(1 year)
- Treatment related mortality(2 years)
- Overall survival(2 years)
- Neutrophil recovery time(From day 0 until the first of 3 consecutive days)
研究者
Fang Zhou
Principal Investigator
Jinan Military General Hospital