Sirolimus Combined With All Trans Retinoic Acid for the Treatment of Auto-Immune Anemia
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- overall response rate
研究概览
简要总结
Autoimmune anemia (AIA), including autoimmune hemolytic anemia (AIHA), EVENs' syndrome (ES), acquired pure red aplastic anemia (PRCA), is a kind of anemia disease mediated by autoimmunity, which can be primary or secondary to other diseases including autoimmune disease, malignant tumor, infection, etc. Glucocorticoid is the first-line treatment. However, the recurrence rate is very high and some patients may not response to steroids, the latter defined as refractory autoimmune anemia (RAIA). Second-line therapies include cyclosporine A (CSA), cyclophosphamide, 6-mercaptopurine, CD20 monoclonal antibody, anti human lymphocyte immunoglobulin (ATG), and even splenectomy. Cyclosporine A is easy to accept while some patients may have side effects such as renal function damage, gingival hyperplasia, hypertension and so on. Other second-line drugs also have many problems, such as low effective rate, slow onset, expensive price, and large side effects, and some patients do not response to these treatments. The refractory/relapsed AIA patients have increased cardiovascular events, increased opportunities for infections, decreased quality of life, and even death. At present, there is still no effective treatment for these patients. Our previous retrospective study showed that sirolimus was effective in cyclosporine refractory PRCA with an effective rate of 70% and slight side effects. In addition, we used sirolimus in refractory AIHA and ES, with an effective rate of 60-70%. However, there are still some non-responsive patients. Recently, it has been reported that all trans retinoic acid (ATRA) combined with danazol was effective in the treatment of refractory immune thrombocytopenic purpura (ITP). Therefore, we plans to combine sirolimus and ATRA in the treatment of refractory AIA to improve the efficacy. Since both sirolimus and ATRA are cheap and have slight side effects, this combination may reduce the economic burden of patients and reduce the side effects related to treatment.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosed as autoimmune anemia (autoimmune hemolytic anemia, pure red aplastic anemia, events syndrome) without organ complications;
- •ineffective, relapsed or intolerant patients who have been treated with at least one kind of sufficient current conventional drug (steroids, CsA, CD20 monoclonal antibody, tacrolimus and others) ;
- •normal cardiac function, liver function (ALT/AST ≤ 3.0 × ULN) and renal function (serum creatinine ≤ 1 × ULN);
- •no secondary disease;
- •unable to accept hematopoietic stem cell transplantation;
- •ECoG score ≤ 2;
- •able to sign the informed consent form.
排除标准
- •failure to make a definite diagnosis;
- •AIA secondary to known diseases such as systemic lupus erythematosus, rheumatoid arthritis, tumor or other inflammatory diseases;
- •severe hepatorenal insufficiency (creatinine, transaminase more than 3 times of the upper limit of normal value);
- •uncontrollable systemic infection or other serious diseases;
- •pregnant or lactating women;
- •patients with mental disease who are unable to sign the informed consent;
- •taking other AIA drugs or stopping the drugs for less than 3 months;
- •allergic to the study drug;
- •participation in other clinical studies;
- •patients in any other circumstances considered unsuitable by the investigator.
研究组 & 干预措施
treatment group
combined sirolimus(serum concentration to be 4-10ng/ml) and ATRA (20mg bid) for at least 6 months
干预措施: sirolimus and ATRA (Drug)
结局指标
主要结局
overall response rate
时间窗: 1 year
overall response rate
rate of side effects
时间窗: 1 year
rates and types of all side effects
次要结局
- frequency of HGB transfusion(through study completion, an average of 1 year)
- change of HGB concentration(through study completion, an average of 1 year)
- time to response(through study completion, an average of 1 year)
- response duration(through study completion, an average of 1 year)
- life quality score (SF 36)(through study completion, an average of 1 year)
- change of bilirubin concentration(through study completion, an average of 1 year)
研究者
Bing Han
Professor
Peking Union Medical College Hospital