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)

Rituximab in Patients With Relapsed or Refractory TTP-HUS

Sponsors

Lead sponsor: Hamilton Health Sciences Corporation

Collaborator: Canadian Apheresis Group
Hoffmann-La Roche
McMaster University

Source McMaster University
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.

Overall Status Unknown status
Start Date December 2007
Completion Date January 2011
Primary Completion Date January 2011
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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 Outcome
Measure Time Frame
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
frequency of relapse 52 weeks
mortality 52 weeks
changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level 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 8 weeks
Enrollment 60
Condition
Intervention

Intervention type: Drug

Intervention name: Rituximab

Description: 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.

Arm group label: Study group

Other name: Rituxan, rituximab

Eligibility

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Overall Contact

Last name: Kathryn E Webert, MD

Phone: 905-521-2100

Phone ext: 76733

Email: [email protected]

Location
facility status contact investigator
Foothills Medical Centre, Calgary Health REgion Apheresis Service | Calgary, Alberta, T2N 2T9, Canada Not yet recruiting John Klassen, MD 403-944-4712 [email protected] John Klassen, MD Principal Investigator
University of Alberta Hospital | Edmonton, Alberta, Canada Not yet recruiting L Larratt, MD Principal Investigator
Vancouver General Hospital | Vancouver, British Columbia, V5Z1M9, Canada Recruiting Paul Yenson, Dr. 604-875-4863 [email protected] Paul Yenson, Dr Principal Investigator
Winnipeg Regional Health Authority, Apheresis Department | Winnipeg, Manitoba, R3E 0T2, Canada Not yet recruiting Cathy Moltzan, MD 204-787-4269 [email protected] Cathy Moltzan, MD Principal Investigator
St. John Regional Hospital | St. John, New Brunswick, E2K5S9, Canada Not yet recruiting Sean Dolan, MD 506-634-1201 Sean Dolan, MD Principal Investigator
Hamilton Health Sciences | Hamilton, Ontario, L8N 3Z5, Canada Recruiting Julie Carruthers 905-525-9140 22942 [email protected] Kathryn E Webert, MD Principal Investigator Ronan Roley, MD Principal Investigator Donald M Arnold, MD Sub-Investigator
London Health Sciences Centre, Westminister Campus | London, Ontario, N6A4G5, Canada Recruiting Clark F William, MD 519-685-8500 57238 [email protected] William F Clark, MD Principal Investigator
Princess Margaret Hospital, ABMT/Apheresis Unit | Toronto, Ontario, M5G2M9, Canada Recruiting David Barth, MD 416-946-4688 [email protected] David Barth, MD Principal Investigator
Hopital Charles Lemoyne | Greenfield Park, Quebec, Canada Not yet recruiting S Fox, MD 450-466-5000 S Fox, MD Principal Investigator
Hopital du Sacre-Coeur de Montreal | Montreal, Quebec, H4J1C5, Canada Not yet recruiting J P Moquin, MD 514-338-2222 3368 [email protected] J P Moquin, MD Principal Investigator
St. Paul's Hospital Apheresis Unit | Saskatoon, Saskatchewan, S7M 0Z9, Canada Recruiting Ahmed Shoker, MD 306-655-5934 [email protected] Ahmed Shoker, MD Principal Investigator
Location Countries

Canada

Verification Date

September 2007

Responsible Party

Name title: Canadian Apheresis Group

Organization: Canadian Apheresis Group

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Study group

Arm group type: Experimental

Description: All patients in the study will be in the study group and will receive rituximab. There is no "control" arm.

Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov