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)
Overview
- Phase
- Phase 2
- Intervention
- Rituximab
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Sponsor
- Hamilton Health Sciences Corporation
- Enrollment
- 60
- Locations
- 11
- Primary Endpoint
- 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.
- Last Updated
- 15 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •any patient 18 years or older diagnosed with relapsed or refractory TTP-HUS requiring therapy
Exclusion Criteria
- •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
Arms & Interventions
Study group
All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.
Intervention: Rituximab
Outcomes
Primary Outcomes
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.
Time Frame: 8 weeks after initiation of therapy
Secondary Outcomes
- 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)