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Rituximab in Patients With Relapsed or Refractory TTP-HUS

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2007 by McMaster University.
Recruitment status was:  Recruiting
Sponsor:
Collaborators:
Canadian Apheresis Group
Hoffmann-La Roche
McMaster University
Information provided by:
McMaster University
ClinicalTrials.gov Identifier:
NCT00531089
First received: September 17, 2007
Last updated: May 18, 2010
Last verified: September 2007
  Purpose
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.

Condition Intervention Phase
Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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. [ Time Frame: 8 weeks after initiation of therapy ] [ Designated as safety issue: No ]

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

Estimated Enrollment: 60
Study Start Date: December 2007
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study group
All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.
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.
Other Name: Rituxan, rituximab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531089

Locations
Canada, Alberta
Foothills Medical Centre, Calgary Health REgion Apheresis Service
Calgary, Alberta, Canada, T2N 2T9
University of Alberta Hospital
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z1M9
Canada, Manitoba
Winnipeg Regional Health Authority, Apheresis Department
Winnipeg, Manitoba, Canada, R3E 0T2
Canada, New Brunswick
St. John Regional Hospital
St. John, New Brunswick, Canada, E2K5S9
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
London Health Sciences Centre, Westminister Campus
London, Ontario, Canada, N6A4G5
Princess Margaret Hospital, ABMT/Apheresis Unit
Toronto, Ontario, Canada, M5G2M9
Canada, Quebec
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J1C5
Canada, Saskatchewan
St. Paul's Hospital Apheresis Unit
Saskatoon, Saskatchewan, Canada, S7M 0Z9
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Canadian Apheresis Group
Hoffmann-La Roche
McMaster University
Investigators
Principal Investigator: Kathryn E Webert, E Hamilton Health Sciences Corporation
Principal Investigator: Ronan Foley, MD Hamilton Health Sciences Corporation
Study Director: Gail Rock, MD Canadian Apheresis Group
Study Director: William Clark, MD University of Western Ontario/London Health Sciences
Study Director: David Barth, MD University of Toronto
  More Information

Responsible Party: Canadian Apheresis Group
ClinicalTrials.gov Identifier: NCT00531089     History of Changes
Other Study ID Numbers: CAG-1 
Study First Received: September 17, 2007
Last Updated: May 18, 2010
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
TTP
thrombotic thrombocytopenic purpura
HUS
hemolytic uremic syndrome
plasma exchange

Additional relevant MeSH terms:
Syndrome
Hemolytic-Uremic Syndrome
Purpura, Thrombocytopenic
Purpura
Hemolysis
Purpura, Thrombotic Thrombocytopenic
Azotemia
Disease
Pathologic Processes
Blood Coagulation Disorders
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhage
Skin Manifestations
Signs and Symptoms
Thrombophilia
Uremia
Kidney Diseases
Urologic Diseases
Anemia, Hemolytic
Anemia
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 06, 2016