International Immune Tolerance Study

December 4, 2009 updated by: New York Presbyterian Hospital

An International Randomised Controlled Trial Of Immune Tolerance Induction

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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

134

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama Birmingham Medical Center
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Mountain States Regional Hemophilia and Thrombosis Center
    • Florida
      • St. Petersburg, Florida, United States, 33701
        • All Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian St. Lukes
      • Peoria, Illinois, United States, 61614
        • Comprehensive Bleeding Disorders Center
    • Indiana
      • Indianapolis, Indiana, United States, 46034
        • Indiana Hemophilia & Thrombosis center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Hospital and Clinic
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
      • Boston, Massachusetts, United States, 02111
        • TUFTS - New England Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health Hospitals
      • East Lansing, Michigan, United States, 48824
        • MSU Centers for Bleeding & Clotting Disorders
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospital Minneapolis
      • Rochester, Minnesota, United States, 55905
        • Mayo Comprehensive Hemophilia Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Newark, New Jersey, United States, 07102
        • Saint Michael's Medical Center
      • Newark, New Jersey, United States, 07102
        • Newark Beth Israel Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Ted R. Montoya Hemophilia Treatment Center
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10021
        • NY Presbyterian Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Columbus, Ohio, United States, 43205
        • Columbus Children's Hospital
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Hospital for Children, Section of Hem/Onc
      • Pittsburgh, Pennsylvania, United States, 15213
        • The Hemophilia Center of Western Pennsylvania
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Portsmouth, Virginia, United States, 23708
        • Naval Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53201
        • Comprehensive Center for Bleeding Disorders

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

No older than 7 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Low-dose treatment (50 FVIII u/kg three times a week).
To be determined at the discretion of the investigator.
50 FVIII u/kg three times a week.
Active Comparator: 2
High-dose treatment (200 FVIII u/kg per day).
To be determined at the discretion of the investigator.
200 FVIII u/kg per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Success-rate and partial success-rate
Time Frame: Up to 69 months
Up to 69 months
The time from the start of ITI to successful tolerance
Time Frame: Up to 33 months
Up to 33 months
The comparative cost-effectiveness of the two treatment arms
Time Frame: Up to 69 months
Up to 69 months
A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days.
Time Frame: Up to 69 months
Up to 69 months
The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
Time Frame: Up to 45 months
Up to 45 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The dose-regimen, success rate and time to ITI,
Time Frame: Up to 69 months
Up to 69 months
The starting inhibitor titre, success rate and time to ITI,
Time Frame: Up to 69 months
Up to 69 months
The peak historical inhibitor titre, success rate and time to ITI,
Time Frame: Up to 69 months
Up to 69 months
The peak inhibitor titre after starting ITI, success rate and time to success,
Time Frame: Up to 69 months
Up to 69 months
The age at the time of inhibitor detection, success-rate and time to success,
Time Frame: Up to 69 months
Up to 69 months
The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.
Time Frame: Up to 69 months
Up to 69 months
The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,
Time Frame: Up to 69 months
Up to 69 months
The effect of interim infections/immunisations, success rate and time to success,
Time Frame: Up to 69 months
Up to 69 months
The effect of treatment interruption, success rate and time to success.
Time Frame: Up to 69 months
Up to 69 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Donna M DiMichele, MD, Weill Cornell Medical College-NY Presybetrian Hospital
  • Principal Investigator: Charles Hay, MD, Manchester Royal Infirmary

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

July 1, 2002

Primary Completion (Anticipated)

December 1, 2010

Study Completion (Anticipated)

December 1, 2012

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 21, 2005

Study Record Updates

Last Update Posted (Estimate)

December 7, 2009

Last Update Submitted That Met QC Criteria

December 4, 2009

Last Verified

October 1, 2009

More Information

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.

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