Sirolimus in the Treatment of Refractory/Relapsed Warm Autoimmune Hemolytic Anemia (AIHA)： a Phase 2 Prospective Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) and complete response rate (CRR)
研究概览
简要总结
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Our previous study of sirolimus in refractory/relapsed AIHA and ES found an effective rate of 80%. Therefore, the investigators plan to explore the efficacy and safety of sirolimus in the treatment of refractory/relapsed wAIHA.
详细描述
Based on the optimal autoantibody-RBC reactivity temperatures, AIHA is classified into warm type, cold type, and mixed type. AIHA can be further classified into primary or secondary in nature. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. The refractory/relapsed wAIHA patients have increased cardiovascular events, increased opportunities for infections, decreased quality of life, and even death. A prospective multi-institutional trial in autoimmune cytopenia found that 8 of 10 patients with AIHA and Evans syndrome respond to sirolimus. Our previous study of sirolimus in refractory/relapsed AIHA and ES also found an effective rate of approximately 80%. Since sirolimus is cheap and accessible, our findings may reduce the economic burden of patients and be a guide on the selection of second-line treatment drugs in refractory/relapsed wAIHA and Evans syndrome.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old.
- •Diagnosed as primary warm autoimmune hemolytic anemia or Evans syndrome (primary or secondary). There is no treatment indication of other systemic involvement in the original disease if secondary.
- •No response to glucocorticoid therapy or recurrence.
- •Baseline liver (ALT, AST) was less than 2 times the normal value.
- •No active infection; Not pregnant or breastfeeding.
- •Agree to sign the consent form.
排除标准
- •Patients with connective tissue disease or other organs involvement
- •Infection or bleeding that cannot be controlled by standard treatment.
- •Active HIV, HCV or HBV infection or cirrhosis or portal hypertension.
- •Progressed uncontrolled malignant tumors and lymphoma
- •Cirrhosis or portal hypertension.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Sirolimus on refractory/relapsed wAIHA
A prospective research of the sirolimus efficiency on refractory/relapsed primary wAIHA patients. Sirolimus dosage: 1-3 mg/d with plasma concentration 4-15ng/mL. Medication time should last at least 6 months. After reaching the optimal response, responders continue to use sirolimus for 1 year, and then gradually reduce the dosage.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Overall response rate (ORR) and complete response rate (CRR)
时间窗: 3,6,12 months
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR).
次要结局
- Number of participants with treatment-related adverse events and the number of relapses(12 months, end of the follow-up)
- Adverse events(3,6,12 months)
- Relapse rate(3,6,12 months)
研究者
Chen Miao
associate professor
Peking Union Medical College Hospital