Rituximab in Patients With Relapsed or Refractory TTP-HUS

Condition(s) targeted: Thrombotic Thrombocytopenic Purpura; Hemolytic Uremic Syndrome

Intervention: Rituximab (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Hamilton Health Sciences

Official(s) and/or principal investigator(s):
Kathryn E Webert, E, Principal Investigator, Affiliation: Hamilton Health Sciences
Ronan Foley, MD, Principal Investigator, Affiliation: Hamilton Health Sciences
Gail Rock, MD, Study Director, Affiliation: Canadian Apheresis Group
William Clark, MD, Study Director, Affiliation: University of Western Ontario/London Health Sciences
David Barth, MD, Study Director, Affiliation: University of Toronto

Overall contact:
Kathryn E Webert, MD, Phone: 905-521-2100, Ext: 76733, Email: webertk@mcmaster.ca

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.

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)

Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome:

proportion of patients with platelet count greater than 150 x 109/L

proportion of patients with LDH < 1.5 X normal

proportion of patients with no requirement for plasma exchange therapy

proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms

clinical response (CR, PR, non-response)

frequency of relapse

mortality

changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level

toxicity and clinical safety as assessed by monitoring of adverse events, laboratory parameters, vital signs during infusion, and immediate tolerability

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Kathryn E Webert, MD, Phone: 905-521-2100, Ext: 76733, Email: webertk@mcmaster.ca

Foothills Medical Centre, Calgary Health REgion Apheresis Service, Calgary, Alberta T2N 2T9, Canada

University of Alberta Hospital, Edmonton, Alberta, Canada

Vancouver General Hospital, Vancouver, British Columbia, Canada

Cancer Care Centre, Winnipeg, Manitoba, Canada

Winnipeg Regional Health Authority, Apheresis Department, Winnipeg, Manitoba R3E 0T2, Canada

St. John Regional Hospital, St. John, New Brunswick E2K5S9, Canada

Queen Elizabeth II health Science Centre, Halifax, Nova Scotia B3H2Y9, Canada

Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

London Health Sciences Centre, Westminister Campus, London, Ontario N6A4G5, Canada

Princess Margaret Hospital, ABMT/Apheresis Unit, Toronto, Ontario M5G2M9, Canada

Sault Ste. Marie Hospital, Sault Ste. Marie, Ontario, Canada

Hopital du Sacre-Coeur de Montreal, Montreal, Quebec H4J1C5, Canada

Hopital Charles Lemoyne, Greenfield Park, Quebec, Canada

Royal University Hospital, Apheresis Unit, Saskatoon, Saskatchewan S7N 0X0, Canada

Starting date: December 2007
Ending date: January 2010
Last updated: September 17, 2007