Title
Rituximab in Patients With Relapsed or Refractory TTP-HUS
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)
Phase
Phase 2Lead Sponsor
Hamilton Health Sciences CorporationStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Thrombotic Thrombocytopenic Purpura Hemolytic Uremic SyndromeIntervention/Treatment
rituximab ...Study Participants
60The 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.
Rituximab will be administered on weeks 1, 2, 3, and 4 at a dose of 375 mg/m2 per infusion. Premedications (prednisone 50 mg, diphenhydramine 50 mg, acetaminophen) will be administered prior to study infusion. Patients will also be treated with plasma exchange as per institution/apheresis centre.
All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.
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 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
