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Rituximab in Patients With Relapsed or Refractory TTP-HUS

Primary Purpose

Thrombotic Thrombocytopenic Purpura, Hemolytic Uremic Syndrome

Status

Unknown status

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Rituximab

About this trial

This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura focused on measuring TTP, thrombotic thrombocytopenic purpura, HUS, hemolytic uremic syndrome, plasma exchange

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Foothills Medical Centre, Calgary Health REgion Apheresis Service
University of Alberta Hospital
Vancouver General HospitalRecruiting
Winnipeg Regional Health Authority, Apheresis Department
St. John Regional Hospital
Hamilton Health SciencesRecruiting
London Health Sciences Centre, Westminister CampusRecruiting
Princess Margaret Hospital, ABMT/Apheresis UnitRecruiting
Hopital Charles Lemoyne
Hopital du Sacre-Coeur de Montreal
St. Paul's Hospital Apheresis UnitRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study group

Arm Description

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

Outcomes

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00531089

First Posted

September 17, 2007

Last Updated

May 18, 2010

Sponsor

Hamilton Health Sciences Corporation

Collaborators

Canadian Apheresis Group, Hoffmann-La Roche, McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT00531089

Brief Title

Rituximab in Patients With Relapsed or Refractory TTP-HUS

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 Type

Interventional

2. Study Status

Record Verification Date

September 2007

Overall Recruitment Status

Unknown status

Study Start Date

December 2007 (undefined)

Primary Completion Date

January 2011 (Anticipated)

Study Completion Date

January 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Hamilton Health Sciences Corporation

Collaborators

Canadian Apheresis Group, Hoffmann-La Roche, McMaster University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombotic Thrombocytopenic Purpura, Hemolytic Uremic Syndrome

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Study group

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan, rituximab

Intervention 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.

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

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

Time Frame

8 weeks

Title

proportion of patients with LDH < 1.5 X normal

Time Frame

8 weeks

Title

proportion of patients with no requirement for plasma exchange therapy

Time Frame

8 weeks

Title

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

Time Frame

8 weeks

Title

clinical response (CR, PR, non-response)

Time Frame

52 weeks

Title

frequency of relapse

Time Frame

52 weeks

Title

mortality

Time Frame

52 weeks

Title

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

Time Frame

8, 12, 24, 52 weeks

Title

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

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kathryn E Webert, MD

Phone

905-521-2100

Ext

76733

webertk@mcmaster.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kathryn E Webert, E

Organizational Affiliation

Hamilton Health Sciences Corporation

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ronan Foley, MD

Organizational Affiliation

Hamilton Health Sciences Corporation

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gail Rock, MD

Organizational Affiliation

Canadian Apheresis Group

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

William Clark, MD

Organizational Affiliation

University of Western Ontario/London Health Sciences

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

David Barth, MD

Organizational Affiliation

University of Toronto

Official's Role

Study Director

Facility Information:

Facility Name

Foothills Medical Centre, Calgary Health REgion Apheresis Service

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 2T9

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

John Klassen, MD

Phone

403-944-4712

john.klassen@calgaryhealthregion.ca

First Name & Middle Initial & Last Name & Degree

John Klassen, MD

Facility Name

University of Alberta Hospital

City

Edmonton

State/Province

Alberta

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

L Larratt, MD

Facility Name

Vancouver General Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z1M9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Paul Yenson, Dr.

Phone

604-875-4863

pyenson@bccancer.bc.ca

First Name & Middle Initial & Last Name & Degree

Lisa Basque

Phone

604-875-4111

Ext

69014

lbasque@bccancer.bc.ca

First Name & Middle Initial & Last Name & Degree

Paul Yenson, Dr

Facility Name

Winnipeg Regional Health Authority, Apheresis Department

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E 0T2

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cathy Moltzan, MD

Phone

204-787-4269

cmoltzan@sbgh.mb.ca

First Name & Middle Initial & Last Name & Degree

Cathy Moltzan, MD

Facility Name

St. John Regional Hospital

City

St. John

State/Province

New Brunswick

ZIP/Postal Code

E2K5S9

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sean Dolan, MD

Phone

506-634-1201

First Name & Middle Initial & Last Name & Degree

Sean Dolan, MD

Facility Name

Hamilton Health Sciences

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 3Z5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Julie Carruthers

Phone

905-525-9140

Ext

22942

carrutj@mcmaster.ca

First Name & Middle Initial & Last Name & Degree

Kathryn E Webert, MD

First Name & Middle Initial & Last Name & Degree

Ronan Roley, MD

First Name & Middle Initial & Last Name & Degree

Donald M Arnold, MD

Facility Name

London Health Sciences Centre, Westminister Campus

City

London

State/Province

Ontario

ZIP/Postal Code

N6A4G5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Clark F William, MD

Phone

519-685-8500

Ext

57238

william.clark@lhsc.on.ca

First Name & Middle Initial & Last Name & Degree

William F Clark, MD

Facility Name

Princess Margaret Hospital, ABMT/Apheresis Unit

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G2M9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Barth, MD

Phone

416-946-4688

david.barth@uhn.on.ca

First Name & Middle Initial & Last Name & Degree

David Barth, MD

Facility Name

Hopital Charles Lemoyne

City

Greenfield Park

State/Province

Quebec

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

S Fox, MD

Phone

450-466-5000

First Name & Middle Initial & Last Name & Degree

S Fox, MD

Facility Name

Hopital du Sacre-Coeur de Montreal

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H4J1C5

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

J P Moquin, MD

Phone

514-338-2222

Ext

3368

jp.moquin@videotron.ca

First Name & Middle Initial & Last Name & Degree

J P Moquin, MD

Facility Name

St. Paul's Hospital Apheresis Unit

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7M 0Z9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ahmed Shoker, MD

Phone

306-655-5934

ahmed.shoker@usask.ca

First Name & Middle Initial & Last Name & Degree

Ahmed Shoker, MD

12. IPD Sharing Statement

Learn more about this trial

Rituximab in Patients With Relapsed or Refractory TTP-HUS

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