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

Sponsors and Collaborators:	Hamilton Health Sciences Canadian Apheresis Group (CAG)
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

Genetics Home Reference related topics: factor V Leiden thrombophilia hemophilia thrombotic thrombocytopenic purpura

Drug Information available for: Prednisone Rituximab Diphenhydramine Diphenhydramine citrate Diphenhydramine hydrochloride Promethazine Promethazine hydrochloride Acetaminophen

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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)

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 ]

Secondary Outcome Measures:

proportion of patients with platelet count greater than 150 x 109/L [ Time Frame: 8 weeks ]
proportion of patients with LDH < 1.5 X normal [ Time Frame: 8 weeks ]
proportion of patients with no requirement for plasma exchange therapy [ Time Frame: 8 weeks ]
proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms [ Time Frame: 8 weeks ]
clinical response (CR, PR, non-response) [ Time Frame: 52 weeks ]
frequency of relapse [ Time Frame: 52 weeks ]
mortality [ Time Frame: 52 weeks ]
changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level [ Time Frame: 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 [ Time Frame: 8 weeks ]

Estimated Enrollment:	60
Study Start Date:	December 2007
Estimated Study Completion Date:	January 2010

Arms	Assigned Interventions
Study group: Experimental 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.

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
Calgary, Alberta, Canada, T2N 2T9
University of Alberta Hospital
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada
Canada, Manitoba
Cancer Care Centre
Winnipeg, Manitoba, Canada
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, Nova Scotia
Queen Elizabeth II health Science Centre
Halifax, Nova Scotia, Canada, B3H2Y9
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
Sault Ste. Marie Hospital
Sault Ste. Marie, Ontario, Canada
Canada, Quebec
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J1C5
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada
Canada, Saskatchewan
Royal University Hospital, Apheresis Unit
Saskatoon, Saskatchewan, Canada, S7N 0X0

Sponsors and Collaborators

Hamilton Health Sciences

Canadian Apheresis Group (CAG)

Investigators

Principal Investigator:	Kathryn E Webert, E	Hamilton Health Sciences
Principal Investigator:	Ronan Foley, MD	Hamilton Health Sciences
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

Study ID Numbers:	CAG-1
Study First Received:	September 17, 2007
Last Updated:	September 17, 2007
ClinicalTrials.gov Identifier:	NCT00531089
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:

TTP
thrombotic thrombocytopenic purpura
HUS
hemolytic uremic syndrome
plasma exchange

Study placed in the following topic categories:

Prednisone
Thrombophilia
Hemostatic Disorders
Purpura, Thrombotic Thrombocytopenic
Purpura, Thrombocytopenic
Hemolytic-Uremic Syndrome
Signs and Symptoms
Promethazine
Thrombocytopenia
Urologic Diseases
Kidney Diseases
Acetaminophen
Azotemia
Purpura
Hemolytic-uremic syndrome

Rituximab
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Anemia
Vascular Diseases
Anemia, Hemolytic
Thrombosis
Thrombotic thrombocytopenic purpura, acquired
Thrombocytopathy
Embolism and Thrombosis
Embolism
Uremia
Diphenhydramine

Additional relevant MeSH terms:

Skin Manifestations
Pathologic Processes
Disease
Immunologic Factors
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Syndrome
Physiological Effects of Drugs
Cardiovascular Diseases
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009