Romiplostim in Combination With Ciclosporin Versus Ciclosporin in the Treatment of Newly Diagnosed Non-severe Aplastic Anemia
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- complete response rate (CRR)
研究概览
简要总结
Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. Treatment options for patients with aplastic anemia are very limited. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the primary endpoint showed an overall response rate of 84% [95% CI 66-95%] at week 27. However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Therefore, we aimed to compare the efficacy and safety of romiplostim in combination with CsA versus CsA monotherapy.
详细描述
Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. Treatment options for patients with aplastic anemia are very limited. By binding to the thrombopoietin (TPO) receptor, thrombopoietin receptor agonists (TPO-RAs) can cause conformational changes in the TPO receptor, activate the JAK2/STATS pathway, and increase megakaryocyte progenitor cells proliferation and platelet production. At present, TPO-RAs including eltrombopag, lusutrombopag, romiplostim, and avatrombopag have been approved by FDA. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, 31 patients with refractory AA were enrolled. The primary endpoint for the proportion of patients who achieved any hematological (platelet, neutrophil, and red blood cell) response at week 27 was 84% [95% CI 66-95%]. At week 53, the three-line response rate was 39% (95% CI 22-58%). However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Since romiplostim and CsA have good safety, if it is proved that the combination of the two drugs is superior to ciclosporin monotherapy, it can quickly improve blood patterns in NSAA, avoid the use of more expensive ATG, and provide some help to reduce the economic burden of AA patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old.
- •Clearly diagnosed as untreated NSAA.
- •At least one of the following conditions was met at the time of enrollment: hemoglobin <90 g/L. Platelet <30×109/L, neutrophils <1.0×109/L.
- •Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value.
- •No active infection; Not pregnant or breastfeeding.
- •Agree to sign the consent form.
- •The Eastern Cancer Collaboration Group (ECOG) score was 0-2.
排除标准
- •Pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS).
- •There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML).
- •PNH clone ≥50%.
- •Had received hematopoietic stem cell transplantation (HSCT) before enrollment.
- •Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks.
- •Infection or bleeding that is not controlled by standard treatment.
- •Allergic to recombinant TPO or Hitrepopar.
- •Active HIV, HCV, HBV infection or cirrhosis, or portal hypertension.
- •Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years.
- •Previous history of thromboembolic events, heart attack or stroke (including antiphospholipid antibody syndrome), and current use of anticoagulants.
- •Women who are pregnant or nursing (lactation).
- •Have participated in other clinical trials within 3 months
研究组 & 干预措施
Romiplostim+CsA
Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L.
Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.
干预措施: Romiplostim (Drug)
Romiplostim+CsA
Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L.
Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.
干预措施: Ciclosporin (Drug)
CsA
Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.
干预措施: Ciclosporin (Drug)
结局指标
主要结局
complete response rate (CRR)
时间窗: 3, 6 months
Proportion of patients who achieved complete response.
overall response rate (ORR)
时间窗: 3, 6 months
Proportion of patients who achieved complete response and partial response.
次要结局
- adverse event rate(3, 6 months)
研究者
Bing Han
Professor
Peking Union Medical College Hospital