Rituximab in Patients With Relapsed or Refractory TTP-HUS - Full Text View

Sponsor:	Hamilton Health Sciences Corporation
Collaborators:	Canadian Apheresis Group Hoffmann-La Roche McMaster University
Information provided by:	McMaster University
ClinicalTrials.gov Identifier:	NCT00531089

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 II

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:

Genetics Home Reference related topics: atypical hemolytic-uremic syndrome factor V Leiden thrombophilia hemophilia MYH9-related disorder prothrombin thrombophilia thrombotic thrombocytopenic purpura

Drug Information available for: Rituximab

U.S. FDA Resources

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
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

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

Contacts

Contact: Kathryn E Webert, MD

905-521-2100 ext 76733

webertk@mcmaster.ca

Locations

Canada, Alberta
Foothills Medical Centre, Calgary Health REgion Apheresis Service	Not yet recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: John Klassen, MD 403-944-4712 john.klassen@calgaryhealthregion.ca
Principal Investigator: John Klassen, MD
University of Alberta Hospital	Not yet recruiting
Edmonton, Alberta, Canada
Principal Investigator: L Larratt, MD
Canada, British Columbia
Vancouver General Hospital	Recruiting
Vancouver, British Columbia, Canada, V5Z1M9
Contact: Paul Yenson, Dr. 604-875-4863 pyenson@bccancer.bc.ca
Contact: Lisa Basque 604-875-4111 ext 69014 lbasque@bccancer.bc.ca
Principal Investigator: Paul Yenson, Dr
Canada, Manitoba
Winnipeg Regional Health Authority, Apheresis Department	Not yet recruiting
Winnipeg, Manitoba, Canada, R3E 0T2
Contact: Cathy Moltzan, MD 204-787-4269 cmoltzan@sbgh.mb.ca
Principal Investigator: Cathy Moltzan, MD
Canada, New Brunswick
St. John Regional Hospital	Not yet recruiting
St. John, New Brunswick, Canada, E2K5S9
Contact: Sean Dolan, MD 506-634-1201
Principal Investigator: Sean Dolan, MD
Canada, Ontario
Hamilton Health Sciences	Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Julie Carruthers 905-525-9140 ext 22942 carrutj@mcmaster.ca
Principal Investigator: Kathryn E Webert, MD
Principal Investigator: Ronan Roley, MD
Sub-Investigator: Donald M Arnold, MD
London Health Sciences Centre, Westminister Campus	Recruiting
London, Ontario, Canada, N6A4G5
Contact: Clark F William, MD 519-685-8500 ext 57238 william.clark@lhsc.on.ca
Principal Investigator: William F Clark, MD
Princess Margaret Hospital, ABMT/Apheresis Unit	Recruiting
Toronto, Ontario, Canada, M5G2M9
Contact: David Barth, MD 416-946-4688 david.barth@uhn.on.ca
Principal Investigator: David Barth, MD
Canada, Quebec
Hopital Charles Lemoyne	Not yet recruiting
Greenfield Park, Quebec, Canada
Contact: S Fox, MD 450-466-5000
Principal Investigator: S Fox, MD
Hopital du Sacre-Coeur de Montreal	Not yet recruiting
Montreal, Quebec, Canada, H4J1C5
Contact: J P Moquin, MD 514-338-2222 ext 3368 jp.moquin@videotron.ca
Principal Investigator: J P Moquin, MD
Canada, Saskatchewan
St. Paul's Hospital Apheresis Unit	Recruiting
Saskatoon, Saskatchewan, Canada, S7M 0Z9
Contact: Ahmed Shoker, MD 306-655-5934 ahmed.shoker@usask.ca
Principal Investigator: Ahmed Shoker, MD

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

No publications provided

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:

Hemolytic-Uremic Syndrome
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Azotemia
Hemolysis
Uremia
Kidney Diseases
Urologic Diseases
Anemia, Hemolytic
Anemia
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders

Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Immune System Diseases
Thrombophilia
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012