Rituximab in Patients With Relapsed or Refractory TTP-HUS

May 18, 2010 updated by: Hamilton Health Sciences Corporation

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)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Not yet recruiting
        • Foothills Medical Centre, Calgary Health REgion Apheresis Service
        • Contact:
        • Principal Investigator:
          • John Klassen, MD
      • Edmonton, Alberta, Canada
        • Not yet recruiting
        • University of Alberta Hospital
        • Principal Investigator:
          • L Larratt, MD
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z1M9
        • Recruiting
        • Vancouver General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Paul Yenson, Dr
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0T2
        • Not yet recruiting
        • Winnipeg Regional Health Authority, Apheresis Department
        • Contact:
        • Principal Investigator:
          • Cathy Moltzan, MD
    • New Brunswick
      • St. John, New Brunswick, Canada, E2K5S9
        • Not yet recruiting
        • St. John Regional Hospital
        • Contact:
          • Sean Dolan, MD
          • Phone Number: 506-634-1201
        • Principal Investigator:
          • Sean Dolan, MD
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Recruiting
        • Hamilton Health Sciences
        • Contact:
        • Principal Investigator:
          • Kathryn E Webert, MD
        • Principal Investigator:
          • Ronan Roley, MD
        • Sub-Investigator:
          • Donald M Arnold, MD
      • London, Ontario, Canada, N6A4G5
        • Recruiting
        • London Health Sciences Centre, Westminister Campus
        • Contact:
        • Principal Investigator:
          • William F Clark, MD
      • Toronto, Ontario, Canada, M5G2M9
        • Recruiting
        • Princess Margaret Hospital, ABMT/Apheresis Unit
        • Contact:
        • Principal Investigator:
          • David Barth, MD
    • Quebec
      • Greenfield Park, Quebec, Canada
        • Not yet recruiting
        • Hopital Charles LeMoyne
        • Contact:
          • S Fox, MD
          • Phone Number: 450-466-5000
        • Principal Investigator:
          • S Fox, MD
      • Montreal, Quebec, Canada, H4J1C5
        • Not yet recruiting
        • Hôpital du Sacré-Coeur de Montreal
        • Contact:
        • Principal Investigator:
          • J P Moquin, MD
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7M 0Z9
        • Recruiting
        • St. Paul's Hospital Apheresis Unit
        • Contact:
        • Principal Investigator:
          • Ahmed Shoker, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Rituxan, rituximab

What is the study measuring?

Primary Outcome Measures

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.
Time Frame: 8 weeks after initiation of therapy
8 weeks after initiation of therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
proportion of patients with platelet count greater than 150 x 109/L
Time Frame: 8 weeks
8 weeks
proportion of patients with LDH < 1.5 X normal
Time Frame: 8 weeks
8 weeks
proportion of patients with no requirement for plasma exchange therapy
Time Frame: 8 weeks
8 weeks
proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms
Time Frame: 8 weeks
8 weeks
clinical response (CR, PR, non-response)
Time Frame: 52 weeks
52 weeks
frequency of relapse
Time Frame: 52 weeks
52 weeks
mortality
Time Frame: 52 weeks
52 weeks
changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level
Time Frame: 8, 12, 24, 52 weeks
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
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hamilton Health Sciences Corporation

Collaborators

Hoffmann-La Roche
McMaster University
Canadian Apheresis Group

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Anticipated)

January 1, 2011

Study Completion (Anticipated)

January 1, 2011

Study Registration Dates

First Submitted

September 17, 2007

First Submitted That Met QC Criteria

September 17, 2007

First Posted (Estimate)

September 18, 2007

Study Record Updates

Last Update Posted (Estimate)

May 19, 2010

Last Update Submitted That Met QC Criteria

May 18, 2010

Last Verified

September 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAG-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Thrombotic Thrombocytopenic Purpura

Clinical Trials on Rituximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe