A Pilot Study of Recombinant Humanized Anti-Interleukin (IL-2) Receptor Antibody (Daclizumab) in Patients With Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Number of Participants With Hematologic Response Following Daclizumab in Patients With Moderate Aplastic Anemia (MAA) and Pure Red Cell Aplasia (PRCA).
研究概览
简要总结
Participants in this study are suffering from rare and serious blood disorders. In aplastic anemia, the bone marrow stops producing red blood cells, platelets, and white blood cells. In pure red cell aplasia, the bone marrow stops producing red cells, and in amegakaryocytic thrombocytopenic purpura, the bone marrow stops producing platelets.
Current treatment approaches for these disorders include bone marrow transplant and/or immunosuppression. However, bone marrow transplant is not always possible, and immunosuppression has serious side effects.
This study will investigate whether daclizumab can be used to treat these disorders. Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells. It has been used successfully in many transplant patients to reduce the rate of organ rejection.
Participants will undergo a complete history and physical examination. A bone marrow aspiration and biopsy will be performed to confirm the type of bone marrow failure. About 5 tablespoons of blood will be drawn for baseline tests and research purposes. Daclizumab will be administered every 2 weeks by vein in a 30-minute infusion. The first dose will be given at NIH and the next four may be given at NIH or by the participant's primary hematologist. The treatment will last 8 weeks. Participants must also see their referring physician or NIH physicians every 2 weeks for blood counts. In the fourth and eighth weeks of the study and at the 3-month follow-up visit, 2 tablespoons of blood will be drawn at NIH. At the 1-month follow-up visit to NIH, 5 tablespoons of blood will be drawn and another bone marrow aspiration and biopsy performed.
Risks from bone marrow aspiration and biopsy and blood draws include discomfort. Daclizumab is usually well-tolerated; however, it may weaken immunity against certain bacteria and viruses.
详细描述
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia; single hematopoietic lineage failures such as pure red cell aplasia, Diamond Blackfan Anemia, agranulocytosis, and amegakaryocytic thrombocytopenic purpura; and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG). However, except for severe aplastic anemia, which has been shown to be appropriately treated with either bone marrow transplantation or a combination of ATG and CSA, single agents or regimens have usually not been applied systematically to other immune-mediated hematologic diseases. In an effort to discover other and especially less toxic treatments for immunologically-mediated bone marrow diseases, we seek to apply a new therapy, a humanized anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb ), to a subset of patients with bone marrow failure. Anti-IL-2R mAb acts against activated lymphocytes, thus sharing an important mechanism of action with ATG. However, the mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals (every 2 weeks).
The primary objective is to test the efficacy of anti-IL-2R mAb (daclizumab), we propose to treat four groups of patients: 1) moderate aplastic anemia, 2) single lineage failure states including pure red cell aplasia or Diamond Blackfan anemia, 3) relapse of severe aplastic anemia and 4) refractory severe aplastic anemia not responding to both horse and rabbit ATG/CsA. Subjects will receive daclizumab once every other week for a total of 5 doses. Patients relapsing after response to initial treatment may be treated with 2 additional courses of daclizumab. In November 2005, the relapsed and refractory severe aplastic anemia arms were closed by the Data and Safety Monitoring Board (DSMB) for lack of efficacy. In October 2008, the moderate aplastic anemia arm was closed by the DSMB when the data was determined sufficient for making statistical inferences regarding the original hypotheses. In October 2008, accrual to the Diamond Blackfan anemia arm was closed by the DSMB for lack of accrual.
The Primary endpoint is hematologic response at 3 months. Secondary endpoints include transfusion dependence, overall survival, life threatening toxicity, transformation-free survival, and response duration.
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
- 2 Years 至 —（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
Daclizumab in participants with a bone marrow failure syndrome
daclizumab, 1 mg/kg, will be given for a total of 5 intravenous infusions. These subjects may be diagnosed with moderate aplastic anemia, pure red cell aplasia, Diamond Blackfan anemia, relapse and refractory severe aplastic anemia will receive treatment. The subjects will be seen and receive the daclizumab infusion biweekly during the treatment period.
干预措施: Daclizumab (Drug)
结局指标
主要结局
Number of Participants With Hematologic Response Following Daclizumab in Patients With Moderate Aplastic Anemia (MAA) and Pure Red Cell Aplasia (PRCA).
时间窗: 3 months
Number of participants with hematologic response at 3 months following Daclizumab, 1 mg/kg, will be given for a total of 5 intravenous infusions to subjects diagnosed with moderate aplastic anemia (MAA), pure red cell aplasia (PRCA), Diamond Blackfan anemia (DBA), relapse and refractory severe aplastic anemia (SAA) will receive treatment. A complete hematologic response will be considered an achievement of normal blood counts. A partial response was defined as any response less than a complete response. The primary endpoint was a hematologic response in at least one affected peripheral blood count parameter, as determined by 3 separate measurements in the first 12 weeks after completion of the infusion.
次要结局
- Number of Participants That no Longer Required Blood Transfusion(5 years)
- Overall Survival(5 years)