Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 8
- 主要终点
- Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
研究概览
简要总结
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma exchange often are helped by later treatment with rituximab. The purpose of this study is to see whether combining low doses of rituximab with plasma exchange will help patients get better sooner and reduce the chance of getting TTP again.
详细描述
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for the treatment of thrombotic thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab may decrease the incidence of a composite primary endpoint (exacerbations or refractory disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess the utility of ADAMST13 as a biomarker for response to therapy and prognosis.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 or greater
- •Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
- •Platelet count of < 80,000 for newly diagnosed patients and < 120,000 for relapsed patients
- •Microangiopathic hemolytic anemia with RBC fragmentation
- •LDH >1 x ULN
- •Subjects who will receive treatment for TTP with plasma exchange
- •Subjects who have not started the 5th plasma exchange
- •Plasma ADAMTS13 activity <10%
排除标准
- •Treatment for TTP within the past 2 months
- •Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli O157:H7 or related organism
- •Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
- •Microangiopathic hemolytic anemia due to a mechanical heart valve
- •Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
- •Organ or stem cell transplant
- •Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
- •Disseminated intravascular coagulation as defined by:
- •a. INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen <100 mg/dl
- •Known congenital TTP.
- •Rituximab within the previous year.
- •HIV history or positive serology
- •History of hepatitis B or positive serology for HBsAg or Anti-HBc
- •Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation
- •Hypersensitivities or allergies to murine and/or humanized antibodies
- •Current participation in trials of investigational therapies or devices, other than central catheters
结局指标
主要结局
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
时间窗: 60 days
Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60.
次要结局
- Number of Days to Durable Treatment Response(60 days)
- Incidence of Relapse(Between 30 days and 2 years)
- Incidence of Durable Treatment Response(60 days)
- Incidence of Death(2 years)
- Treatment-related Adverse Events(2 years)
- Months to Relapse(2 years)