A Randomized, Case Controlled Clinical Trial Evaluating the Efficiency and Safety of Luspatercept Plus Cyclosporine Versus Cyclosporine in Newly Diagnosed Transfusion Independent Non-severe Aplastic Anemia (NSAA).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- overall response rate (ORR)
研究概览
简要总结
Aplastic anemia (AA) is a rare bone marrow failure disease characterized by bone marrow hypocellularity and peripheral blood pancytopenia. AA is divided into severe AA (SAA) and non-severe AA (NSAA) based on the degree of cytopenia. The first line therapy for SAA or transfusion dependent NSAA is either immunosuppression therapy (IST) or hematopoietic stem cell transplantation (HSCT). Little attention has been paid to patients with anemia but not transfusion dependent, whose quality of life is significantly impaired due to the anemia and other complications.
详细描述
Recombined human erythropoietin (rhEPO) has been shown to increase the erythroid response and response rate when combined with IST for patients with newly diagnosed AA, either SAA or NSAA. Different from rhEPO, luspatercept is a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands and enhances late-stage erythropoiesis, and has been shown the promising efficiency in the erythropoiesis in patients with lower risk myelodysplastic syndrome (MDS) in the phase II and III clinical trials. This randomized control study aimed to compare the 6-month efficacy and safety of the combination of luspatercept and cyclosporine versus cyclosporine monotherapy in patients with newly diagnosed transfusion independent NSAA.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age≥18 year-old;
- •hemoglobin level between 60g/L~10 g/dL;
- •newly diagnosed patients have at least one of the followings: #absolute neutrophil count <1.5×109/L, #platelet count < 30×109/L, # hemoglobin level < 100g/L;
- •with normal baseline liver and kidney function;
- •with no active infection; are not pregnant or nursing;
- •agree to sign consent forms;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
排除标准
- •Congenital aplastic anemia;
- •Presence of chromosomal aberration;
- •Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics;
- •Presence with PNH clone ≥50%;
- •Patients received HSCT before;
- •Uncontrolled infection or bleeding with standard treatment;
- •Allergic to luspatercept CsA or accessories;
- •HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension;
- •Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site, unstable angina pectoris, uncontrolled hypertension(>180/100mmHg)#pulmonary artery hypertension;
- •Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin;
- •Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
- •Pregnant or nursing (lactating) woman;
- •Have attended other clinical trials within 3 months
研究组 & 干预措施
efficiency and safety in luspatercept plus cyclosporine
luspatercept is at a dose of 1.0 mg per kilogram of body weight, administered subcutaneously every 3 weeks，and cyclosporine is at a dose of 3~5mg/kg /day for at least 6 months.
干预措施: Luspatercept (Drug)
efficiency and safety in luspatercept plus cyclosporine
luspatercept is at a dose of 1.0 mg per kilogram of body weight, administered subcutaneously every 3 weeks，and cyclosporine is at a dose of 3~5mg/kg /day for at least 6 months.
干预措施: Cyclosporine (Drug)
controll group in cyclosporine alone
cyclosporine is at a dose of 3~5mg/kg /day for at least 6 months.
干预措施: Cyclosporine (Drug)
结局指标
主要结局
overall response rate (ORR)
时间窗: 6 month
Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR); HR defined as a hemoglobin increase from baseline of ≥1.5 g/dL for ≥2 weeks (in the absence of RBC transfusions)
次要结局
- Hematologic response-erythroid（HR-E)(6 month)
- side effects(1 year)
- predictive factors(6 month)
研究者
Bing Han
professor
Peking Union Medical College Hospital