A Phase II Study Evaluating the Efficacy of Rituximab in the Management of Patients With Relapsed/Refractory Thrombotic Thrombocytopenic Purpura (TTP) - Hemolytic Uremic Syndrome (HUS)
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 11
- 主要终点
- The proportion of patients achieving all: (1) platelet count >150x109/L; (2) LDH < 1.5 x normal; (3) no requirement for plasma exchange therapy; (4) asymptomatic.
研究概览
简要总结
The general objective of this study is to assess the efficacy and safety of Rituximab in the management of patients with refractory or relapsed thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). There have been several case reports and case series describing the use of Rituximab in patients with TTP-HUS; however its use has not been studied in a large trial. It is hypothesized that Rituximab may ameliorate the severity of certain cases of TTP-HUS by decreasing the number of activity of B-cells which may result in decreased production of the ADAMTS13 protease inhibitor. Patients with TTP-HUS not responding to standard therapy or patients with relapsed disease may have particular benefit. Treatments that decrease the frequency of relapse or shorten the time to remission of TTP-HUS will be of benefit by decreasing the need for blood product support.
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
- •any patient 18 years or older diagnosed with relapsed or refractory TTP-HUS requiring therapy
排除标准
- •alternate cause of hemolytic microangiopathy (evidence of DIC, malignant hypertension, vasculitis, anti-phospholipid antibody syndrome, post-partum acute renal failure)
- •congenital or familial TTP
- •TTP occuring post-stem cell, bone marrow, or solid organ transplant
- •drug-induced TTP
- •pregnancy or breast-feeding
- •history of hepatitis B or C infection
- •prior rituximab treatment
- •active or metastatic cancer
- •other causes of thrombocytopenia such as ITP, myelodysplastic syndrome, confirmed or suspected drug-induced thrombocytopenia
- •refusal to receive blood products
- •hypersensitivity to blood products, plasma products, murine proteins, or any component of the Rituximab formulation
- •geographic inaccessibility
- •co-morbid illness limiting life expectancy to less than 2 months independent of TTP
- •failure to provide written informed consent
研究组 & 干预措施
Study group
All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.
干预措施: Rituximab (Drug)
结局指标
主要结局
The proportion of patients achieving all: (1) platelet count >150x109/L; (2) LDH < 1.5 x normal; (3) no requirement for plasma exchange therapy; (4) asymptomatic.
时间窗: 8 weeks after initiation of therapy
次要结局
- proportion of patients with platelet count greater than 150 x 109/L(8 weeks)
- proportion of patients with LDH < 1.5 X normal(8 weeks)
- proportion of patients with no requirement for plasma exchange therapy(8 weeks)
- proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms(8 weeks)
- clinical response (CR, PR, non-response)(52 weeks)
- frequency of relapse(52 weeks)
- mortality(52 weeks)
- changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level(8, 12, 24, 52 weeks)
- toxicity and clinical safety as assessed by monitoring of adverse events, laboratory parameters, vital signs during infusion, and immediate tolerability(8 weeks)