Hemolytic Uremic Syndrome, Thrombotic Thrombocytopenic Purpura
Conditions
Keywords
TTP, thrombotic thrombocytopenic purpura, HUS, hemolytic uremic syndrome, plasma exchange
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.
Interventions
DRUGRituximab
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.
Sponsors
Canadian Apheresis Group
Hoffmann-La Roche
McMaster University
Hamilton Health Sciences Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| proportion of patients with platelet count greater than 150 x 109/L | 8 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 |
| frequency of relapse | 52 weeks |
Countries
Canada
Contacts
Primary ContactKathryn E Webert, MD
Outcome results
None listed