Rituximab in Patients With Relapsed or Refractory TTP-HUS

Phase 2

• Conditions: Thrombotic Thrombocytopenic Purpura; Hemolytic Uremic Syndrome
• Interventions: Drug: Rituximab

• Registration Number: NCT00531089
• Lead Sponsor: Hamilton Health Sciences Corporation

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2007-09
• Study First Submitted: 2007-09-17
• Study First Submitted QC: 2007-09-17
• Study First Posted: 2007-09-18
• Study Start: 2007-12
• Last Update Submitted: 2010-05-18
• Last Update Posted: 2010-05-19
• Primary Completion: 2011-01
• Study Completion: 2011-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study group	Rituximab	All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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
toxicity and clinical safety as assessed by monitoring of adverse events, laboratory parameters, vital signs during infusion, and immediate tolerability	8 weeks

Trial Locations

Locations (11)

Foothills Medical Centre, Calgary Health REgion Apheresis Service; 🇨🇦 Calgary, Alberta, Canada

Hopital Charles Lemoyne; 🇨🇦 Greenfield Park, Quebec, Canada

Hopital du Sacre-Coeur de Montreal; 🇨🇦 Montreal, Quebec, Canada

St. Paul's Hospital Apheresis Unit; 🇨🇦 Saskatoon, Saskatchewan, Canada

Winnipeg Regional Health Authority, Apheresis Department; 🇨🇦 Winnipeg, Manitoba, Canada

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

St. John Regional Hospital; 🇨🇦 St. John, New Brunswick, Canada

Princess Margaret Hospital, ABMT/Apheresis Unit; 🇨🇦 Toronto, Ontario, Canada

London Health Sciences Centre, Westminister Campus; 🇨🇦 London, Ontario, Canada

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada