Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- ORR at 6 Months
研究概览
简要总结
This is a randomized, open-label, phase II study to compare the efficacy of eltrombopag combined with tacrolimus to eltrombopag alone in Chinese subjects with refractory or relapsed aplastic anemia. The safety would also be evaluated. Patients would be randomized to receive eltrombopag alone or eltrombopag combined with tacrolimus. Treatment with eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with the target trough concentration of 4-10 ng/mL throughout the study. The hematological response rate and safety will be recorded and compared at 3, 6 months and 1 year after starting the study treatment (Week 13, 26 and 52).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with a previous diagnosis of aplastic anemia and had no response or relapsed following at least one treatment course in a period time of ≥ 6 months of immunosuppression containing CsA or CsA+anti-thymocyte globulin (ATG);
- •Current diagnosis of aplastic anemia by bone marrow biopsy;
- •did not receive HSCT nor were HSCT candidates;
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
- •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.
- •Subjects are able to understand and comply with protocol requirements and instructions and have signed and dated informed consent.
排除标准
- •Congenital aplastic anemia;
- •Presence of chromosomal aberration;
- •Evidence of a clonal hematologic bone marrow disorder on cytogenetics;
- •Have any concomitant malignancies and must be fully recovered from treatment for any other malignancy and have been disease-free for 5 years;
- •AST or ALT ≥3 times the upper limit of normal;
- •Serum creatinine, total bilirubin, or alkaline phosphatase >1.5 x ULN;
- •Cardiac disorder (NYHA) functional classification Grade II/III/IV;
- •Past history of thromboembolic event (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
- •Infection not adequately responding to appropriate therapy;
- •Other known or suspected underlying primary immunodeficiency;
- •Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin) receptor agonist;
- •Pregnant or nursing (lactating) woman;
研究组 & 干预措施
Eltrombopag
Eltrombopag and the placebo would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved.
干预措施: Placebo (for Tacrolimus) (Drug)
Eltrombopag + Tacrolimus
Eltrombopag and tacrolimus would be applied. Eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with the target trough concentration of 4-10 ng/mL throughout the study.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
ORR at 6 Months
时间窗: Week 26
Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26
次要结局
- ORR at 3 Months(Week 14)
- Changes in Platelet in the Absence of Platelet Transfusion(Week 26)
- Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia(12 months)
- Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion(Week 26)
- Duration of hematologic response(by 6 months (all patients), at 24 months (responders only))
研究者
Bing Han
Professor
Peking Union Medical College Hospital