Rituximab in Patients With Relapsed or Refractory TTP-HUS

NCT00531089 | Unknown Phase 2 DMC

• 1 other identifier: CAG-1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 11

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.

Conditions

Thrombotic Thrombocytopenic Purpura; Hemolytic Uremic Syndrome

Keywords

TTP; thrombotic thrombocytopenic purpura; HUS; hemolytic uremic syndrome; plasma exchange

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

• 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

• clinical response (CR, PR, non-response)

  52 weeks

Study Arms (1)

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

Interventions

Rituximab DRUG

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.

Also known as: Rituxan, rituximab

Study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• any patient 18 years or older diagnosed with relapsed or refractory TTP-HUS requiring therapy

You may not qualify if:

• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• Canadian Apheresis Group: collaborator
• Hoffmann-La Roche: collaborator
• McMaster University: collaborator

Study Sites (11)

Foothills Medical Centre, Calgary Health REgion Apheresis Service

Calgary, Alberta, T2N 2T9, Canada

NOT YET RECRUITING

University of Alberta Hospital

Edmonton, Alberta, Canada

NOT YET RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z1M9, Canada

RECRUITING

Winnipeg Regional Health Authority, Apheresis Department

Winnipeg, Manitoba, R3E 0T2, Canada

NOT YET RECRUITING

St. John Regional Hospital

Saint John, New Brunswick, E2K5S9, Canada

NOT YET RECRUITING

Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

London Health Sciences Centre, Westminister Campus

London, Ontario, N6A4G5, Canada

RECRUITING

Princess Margaret Hospital, ABMT/Apheresis Unit

Toronto, Ontario, M5G2M9, Canada

RECRUITING

Hopital Charles Lemoyne

Greenfield Park, Quebec, Canada

NOT YET RECRUITING

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J1C5, Canada

NOT YET RECRUITING

St. Paul's Hospital Apheresis Unit

Saskatoon, Saskatchewan, S7M 0Z9, Canada

RECRUITING

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic; Hemolytic-Uremic Syndrome

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kathryn E Webert, E

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

• Ronan Foley, MD

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Central Study Contacts

Kathryn E Webert, MD

CONTACT

905-521-2100; webertk@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 17, 2007
• First Posted: September 18, 2007
• Study Start: December 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: May 19, 2010

Record last verified: 2007-09

Locations

CA (11)