International Immune Tolerance Study

Hemophilia A With Inhibitors Clinical Trial

Official title:

An International Randomised Controlled Trial Of Immune Tolerance Induction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00212472
• Other study ID #: ITI
• Status: Terminated
• Phase: N/A
• First received: September 13, 2005
• Last updated: December 4, 2009
• Start date: July 2002
• Est. completion date: December 2012

Study information

• Verified date: October 2009
• Source: New York Presbyterian Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see if a low-dose arm or a high dose-arm of immune tolerance is more effective in eliminating inhibitors in patients with hemophilia A.

Description:

Subjects will be randomized into a low-dose or high-dose immune tolerance regimen and this study will compare the success rates, the time to achieve tolerance,the complications and the cost of both regimens.It will also aim to identify predictors of successful immune tolerance.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 134
• Est. completion date: December 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 7 Years

Eligibility

Inclusion Criteria:

• Severe hemophilia A (FVIII level <1%).

• A maximum historical inhibitor titer of between 5 BU and 200 BU that must be confirmed once prior to the beginning of ITI.

• The inhibitor titer should be <10 BU at the start of ITI, confirmed once.

• The inhibitor must be present for <24 months when ITI begins.

• Maximum age of 7 at the start of ITI.

• Willingness to comply with the protocol.

Exclusion Criteria:

• Moderate or mild hemophilia A (FVIII level >1%).

• Spontaneous disappearance of the inhibitor prior to ITI.

• Historical maximum inhibitor titer <5 BU or > 200 BU before starting ITI.

• Inhibitor titer > 10 BU at the start of ITI.

• Inhibitor present for more than 24 months before starting ITI.

• Systemic immunomodulatory drug therapy during immune tolerance e.g. corticosteroids (< 5 days every 2 months maximum dose 2 mg/kg or 60 mg/day), azathioprine, cyclophosphamide, high-dose immunoglobulin or the use of a protein A column or plasmapheresis.

• Age > 7 years at the start of ITI.

• Inability or unwillingness to comply with the protocol.

• Previous attempt at ITI.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitors

Intervention

Drug:
• Factor VIII concentrates
To be determined at the discretion of the investigator.

Other:
• Low-dose treatment
50 FVIII u/kg three times a week.
• High-dose treatment
200 FVIII u/kg per day.

Locations

Country	Name	City	State
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Ted R. Montoya Hemophilia Treatment Center	Albuquerque	New Mexico
United States	University of Michigan Health Hospitals	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Mountain States Regional Hemophilia and Thrombosis Center	Aurora	Colorado
United States	University of Alabama Birmingham Medical Center	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Rush Presbyterian St. Lukes	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	MSU Centers for Bleeding & Clotting Disorders	East Lansing	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center	Houston	Texas
United States	Indiana Hemophilia & Thrombosis Center	Indianapolis	Indiana
United States	Kansas City Regional Hemophilia Center-The Children's Mercy Hospital	Kansas City	Missouri
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Comprehensive Center for Bleeding Disorders	Milwaukee	Wisconsin
United States	Children's Hospital Minneapolis	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Mount Sinai Medical Center	New York	New York
United States	NY Presbyterian Hospital	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Children's Hospital of Orange County	Orange	California
United States	Comprehensive Bleeding Disorders Center	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children, Section of Hem/Onc	Philadelphia	Pennsylvania
United States	The Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Naval Medical Center	Portsmouth	Virginia
United States	Mayo Comprehensive Hemophilia Center	Rochester	Minnesota
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	All Children's Hospital	St. Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
New York Presbyterian Hospital	Central Manchester University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success-rate and partial success-rate		Up to 69 months	No
Primary	The time from the start of ITI to successful tolerance		Up to 33 months	No
Primary	The comparative cost-effectiveness of the two treatment arms		Up to 69 months	No
Primary	A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days.		Up to 69 months	Yes
Primary	The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.		Up to 45 months	No
Secondary	The dose-regimen, success rate and time to ITI,		Up to 69 months	No
Secondary	The starting inhibitor titre, success rate and time to ITI,		Up to 69 months	No
Secondary	The peak historical inhibitor titre, success rate and time to ITI,		Up to 69 months	No
Secondary	The peak inhibitor titre after starting ITI, success rate and time to success,		Up to 69 months	No
Secondary	The age at the time of inhibitor detection, success-rate and time to success,		Up to 69 months	No
Secondary	The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.		Up to 69 months	No
Secondary	The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,		Up to 69 months	No
Secondary	The effect of interim infections/immunisations, success rate and time to success,		Up to 69 months	No
Secondary	The effect of treatment interruption, success rate and time to success.		Up to 69 months	No