Rituximab in Patients With Relapsed or Refractory TTP-HUS

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Thrombotic Thrombocytopenic Purpura, Hemolytic Uremic Syndrome

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>All patients in the study will be in the study group and will receive rituximab. There is no control arm. | Drug: Rituximab<br>* 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.<br>* Other names: Rituxan, rituximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 8 weeks after initiation of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTP, thrombotic thrombocytopenic purpura, HUS, hemolytic uremic syndrome, plasma exchange