International Immune Tolerance Study
- Conditions
- Hemophilia A With Inhibitors
- Interventions
- Drug: Factor VIII concentratesOther: Low-dose treatmentOther: High-dose treatment
- Registration Number
- NCT00212472
- Lead Sponsor
- New York Presbyterian Hospital
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 134
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Factor VIII concentrates Low-dose treatment (50 FVIII u/kg three times a week). 1 Low-dose treatment Low-dose treatment (50 FVIII u/kg three times a week). 2 Factor VIII concentrates High-dose treatment (200 FVIII u/kg per day). 2 High-dose treatment High-dose treatment (200 FVIII u/kg per day).
- Primary Outcome Measures
Name Time Method Success-rate and partial success-rate Up to 69 months The time from the start of ITI to successful tolerance Up to 33 months The comparative cost-effectiveness of the two treatment arms 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. Up to 69 months The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI. Up to 45 months
- Secondary Outcome Measures
Name Time Method The dose-regimen, success rate and time to ITI, Up to 69 months The starting inhibitor titre, success rate and time to ITI, Up to 69 months The peak historical inhibitor titre, success rate and time to ITI, Up to 69 months The peak inhibitor titre after starting ITI, success rate and time to success, Up to 69 months The age at the time of inhibitor detection, success-rate and time to success, Up to 69 months The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI. Up to 69 months The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success, Up to 69 months The effect of interim infections/immunisations, success rate and time to success, Up to 69 months The effect of treatment interruption, success rate and time to success. Up to 69 months
Trial Locations
- Locations (39)
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
St. Christopher's Hospital for Children, Section of Hem/Onc
🇺🇸Philadelphia, Pennsylvania, United States
Naval Medical Center
🇺🇸Portsmouth, Virginia, United States
Comprehensive Center for Bleeding Disorders
🇺🇸Milwaukee, Wisconsin, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Ted R. Montoya Hemophilia Treatment Center
🇺🇸Albuquerque, New Mexico, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
NY Presbyterian Hospital
🇺🇸New York, New York, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Columbus Children's Hospital
🇺🇸Columbus, Ohio, United States
Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Rush Presbyterian St. Lukes
🇺🇸Chicago, Illinois, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
The Hemophilia Center of Western Pennsylvania
🇺🇸Pittsburgh, Pennsylvania, United States
Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
🇺🇸Houston, Texas, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Children's Hospital Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Mayo Comprehensive Hemophilia Center
🇺🇸Rochester, Minnesota, United States
Mountain States Regional Hemophilia and Thrombosis Center
🇺🇸Aurora, Colorado, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
University of Alabama Birmingham Medical Center
🇺🇸Birmingham, Alabama, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
All Children's Hospital
🇺🇸St. Petersburg, Florida, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Comprehensive Bleeding Disorders Center
🇺🇸Peoria, Illinois, United States
Indiana Hemophilia & Thrombosis Center
🇺🇸Indianapolis, Indiana, United States
Tulane University Hospital and Clinic
🇺🇸New Orleans, Louisiana, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Michigan Health Hospitals
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
MSU Centers for Bleeding & Clotting Disorders
🇺🇸East Lansing, Michigan, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States