Rituximab in Patients With Relapsed or Refractory TTP-HUS

Thrombotic Thrombocytopenic Purpura Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00531089
• Other study ID #: CAG-1
• Status: Recruiting
• Phase: Phase 2
• First received: September 17, 2007
• Last updated: May 18, 2010
• Start date: December 2007
• Est. completion date: January 2011

Study information

• Verified date: September 2007
• Source: McMaster University
• Contact: Kathryn E Webert, MD
• Phone: 905-521-2100
• Email: webertk[@]mcmaster.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Azotemia
• Hemolysis
• Hemolytic Uremic Syndrome
• Hemolytic-Uremic Syndrome
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

Drug:
• Rituximab
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.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre, Calgary Health REgion Apheresis Service	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	London Health Sciences Centre, Westminister Campus	London	Ontario
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	St. Paul's Hospital Apheresis Unit	Saskatoon	Saskatchewan
Canada	St. John Regional Hospital	St. John	New Brunswick
Canada	Princess Margaret Hospital, ABMT/Apheresis Unit	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Winnipeg Regional Health Authority, Apheresis Department	Winnipeg	Manitoba

Sponsors (4)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	Canadian Apheresis Group, Hoffmann-La Roche, McMaster University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	proportion of patients with platelet count greater than 150 x 109/L		8 weeks	No
Secondary	proportion of patients with LDH < 1.5 X normal		8 weeks	No
Secondary	proportion of patients with no requirement for plasma exchange therapy		8 weeks	No
Secondary	proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms		8 weeks	No
Secondary	clinical response (CR, PR, non-response)		52 weeks	No
Secondary	frequency of relapse		52 weeks	No
Secondary	mortality		52 weeks	No
Secondary	changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level		8, 12, 24, 52 weeks	No
Secondary	toxicity and clinical safety as assessed by monitoring of adverse events, laboratory parameters, vital signs during infusion, and immediate tolerability		8 weeks	Yes