A Multicenter, Single-arm Clinical Study of the Efficacy and Safety of CSA in Combination With Avatrombopag for the Treatment of Primary Treatment of Severe Aplastic Anemia in the Elderly
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- OR rate at 24 weeks of treatment
研究概览
简要总结
This is a multicenter, single-arm clinical study. The objective was to evaluate the efficacy and safety of CSA in combination with Avatrombopag in elderly patients with very/sever aplastic anemia treated for the first time. The design was: cyclosporine 3 mg/kg orally in two divided doses, with cyclosporine trough concentrations maintained at 200-250 ng/ml for 3 months to achieve maximum efficacy, and Avatrombopag, which was administered in two dose groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks. Forty patients are expected to be enrolled in each dose group, and a total of 80 patients are expected to be enrolled if both dose groups are conducted. Evaluation endpoint: OR rate at 24 weeks of treatment.
详细描述
This is a multicenter, single-arm clinical study to evaluate the efficacy and safety of CSA combined with Avatrombopag. The patients are older than 60 years with diagnosis of very sever/sever aplastic anemia(V/SAA) without treatment before.
CSA is started at 3 mg/kg orally in two doses. Concentrations maintained at 200-250 ng/ml to achieve maximum efficacy and then tapered by 25 mg every 3 months; Avatrombopag: two dosing groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks；Each dose group is expected to include 40 patients each. If the 40 mg dose group trial meets the desired trial objectives, the 60 mg dose group trial will not be conducted, and if the 40 mg dose group does not meet the desired trial objectives, the 60 mg dose group trial will be continued. A total of 80 patients were expected to be included if both dose groups were conducted.Overall response rate at 24 weeks of treatment and adverse events are the evaluation endpoint.Secondary study endpoints were: CRR and ORR at 12 and 52 weeks of treatment, CRR at 24 weeks, survival, and clonal evolution in follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •elderly patients with V/SAA with a definite diagnosis.
- •age greater than 60 years, male or female.
- •Subjects must complete all screening assessments as outlined in the trial protocol.
- •Able to swallow or administer the drug orally.
- •Cannot tolerate or refuse ATG therapy.
- •No prior treatment with cyclosporine, tacrolimus or hormones or treatment for no more than 2 weeks.
- •No prior application of TPO receptor agonists (including Thrombopoietin, Eltrombopag, Hetrombopag, etc.) or application of TPO receptor agonists for treatment with ≤ 5 total doses and ≤ 7 days of TPO receptor agonist drugs such as Eltrombopag, Hetrombopag, etc.
- •Informed consent must be signed prior to the start of all specific study procedures, in consideration of the patient's condition, or by a member of the patient's immediate family if the patient's signature is not conducive to the treatment of the condition.
排除标准
- •No subject shall be enrolled in this study if he/she meets any of the following criteria.
- •known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of allogeneic cytopenias and bone marrow hypoproliferative disorders (e.g. hemolytic PNH, hypoproliferative MDS/AML, autoantibody-mediated allogeneic cytopenias, etc.);
- •Patients with uncontrolled bleeding and/or infection despite standard treatment.
- •patients with previous history of hematopoietic stem cell transplantation;
- •previous history of thrombosis.
- •Patients with concurrent malignancy or potential cancer on immunosuppressive therapy.
- •Those who are considered unsuitable for enrollment by the investigator.
研究组 & 干预措施
CSA + Avatrombopag
cyclosporine 3 mg/kg orally in two doses, with cyclosporine trough concentrations maintained at 200-250 ng/ml for 3 months to achieve maximum efficacy and then tapered by 25 mg every 3 months; Avatrombopag: two dosing groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks.If the 40 mg dose group trial meets the desired trial objectives, the 60 mg dose group trial will not be conducted.
干预措施: Avatrombopag (Drug)
结局指标
主要结局
OR rate at 24 weeks of treatment
时间窗: 24 weeks of treatment
Percentage of the total number of patients receiving treatment who received a response at 24 weeks of treatment
Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 24 weeks of treatment
时间窗: 24 weeks of treatment
Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation at 24 weeks
时间窗: 24 weeks of treatment
% of patients with transformation to PNH or MDS,AML, or other disease
次要结局
- OR rate and CR rate at 12 weeks(12 weeks of treatment)
- Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks(12 weeks of treatment)
- Percentage of patients with transformation at 12 weeks(12 weeks of treatment)
研究者
Fengkui Zhang
Director of Anemia Treatment Center
Institute of Hematology & Blood Diseases Hospital, China