Treatment of Severe Aplastic Anemia With Combined Immunosuppression: Antithymocyte Globulin (ATG) and Cyclosporine A (CSA), and Mycophenolate Mofetil (MMF)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- reduction in 24-month relapse
研究概览
简要总结
This study will test the safety and effectiveness of a combination of three drugs in treating severe aplastic anemia and preventing its recurrence. Two drugs used in this trial ATG and cyclosporine are standard combination therapy for aplastic anemia. This study will try to improve this therapy in three ways: 1) by altering the drug regimen to allow the drugs to work better; 2) by reducing the risk of kidney damage; and 3) by adding a third drug mycophenolate mofetil to try to prevent disease relapse.
Patients with severe aplastic anemia who do not have a suitable bone marrow donor or who decline bone marrow transplantation may participate in this study. Patients will have a skin test for ATG allergy, chest X-ray, blood test, and bone marrow aspiration before treatment begins. ATG will then be started, infused through a vein continuously for 4 days. Ten days after ATG is stopped, cyclosporine treatment will begin, taken twice a day by mouth in either liquid or capsule form and will continue for 6 months. Also, in the first 2 weeks of treatment, patients will be given a full dose of corticosteroid (prednisone) to prevent serum sickness that could develop as a side effect of ATG therapy. The dosage will be decreased after that. Mycophenolate will be started at the same time as ATG, in two daily doses by mouth, and will continue for 18 months.
Patients will be hospitalized at the beginning of the study. During this time, blood will be drawn at 3-week intervals and a bone marrow examination will be repeated 3 months after treatment has begun. Additional tests, including X-rays may be required. After hospital discharge, patients will be followed on an outpatient basis at 3-month intervals. The patients own physician will perform blood tests weekly and kidney and liver function tests every 2 weeks during cyclosporine therapy. Transfusions may be required initially.
详细描述
Severe acquired aplastic anemia (SAA) has a poor prognosis if untreated. Bone marrow transplantation is available to only a minority of patients due to lack of a matched sibling donor, advanced age of the patient, or cost. Clinical studies at NIH and elsewhere have demonstrated excellent response rates and improved survival with immunosuppressive treatments. Laboratory data implicate underlying cytotoxic T-lymphocyte-mediated suppression of hematopoiesis as the likely proximal cause of disease in most patients. In earlier clinical protocols we treated SAA with cyclosporine A (CSA) (86-H-0007), antithymocyte globulin (ATG) (87-H-0124), and combined ATG and CSA (90-H-0146). While intensive immunosuppression is most effective, relapse is common and some patients also develop second hematologic complications like myelodysplasia. In this protocol, we modify our regimen by delaying the introduction of cyclosporine to promote ATG tolerizing effects and adding mycophenolate mofetil (MMF), a new agent that, like ATG may be relatively specific for activated lymphocytes, in an effort to reduce the high relapse rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
single arm
ATG 40 mg/kg/d for 4 d; CsA 2 weeks after at 12 mg/kg/d for 6 months. MMF starting on first day of ATG at 600 mg/m2 twice daily for 18 months
干预措施: Cyclosporine A (Drug)
single arm
ATG 40 mg/kg/d for 4 d; CsA 2 weeks after at 12 mg/kg/d for 6 months. MMF starting on first day of ATG at 600 mg/m2 twice daily for 18 months
干预措施: ATG (Drug)
single arm
ATG 40 mg/kg/d for 4 d; CsA 2 weeks after at 12 mg/kg/d for 6 months. MMF starting on first day of ATG at 600 mg/m2 twice daily for 18 months
干预措施: MMF (Drug)
single arm 2
ATG at 40 mg/kg/day for 4 days; MMF at 600 mg/m2 twice daily for 18 months and CsA at 12 mg/kg/day for 6 months starting 2 weeks after ATG and MMF
干预措施: Cyclosporine A (Drug)
single arm 2
ATG at 40 mg/kg/day for 4 days; MMF at 600 mg/m2 twice daily for 18 months and CsA at 12 mg/kg/day for 6 months starting 2 weeks after ATG and MMF
干预措施: ATG (Drug)
single arm 2
ATG at 40 mg/kg/day for 4 days; MMF at 600 mg/m2 twice daily for 18 months and CsA at 12 mg/kg/day for 6 months starting 2 weeks after ATG and MMF
干预措施: MMF (Drug)
结局指标
主要结局
reduction in 24-month relapse
时间窗: 24 months
reduction in 24-month relapse
次要结局
未报告次要终点