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

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
134

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 1
Low-dose treatment (50 FVIII u/kg three times a week).
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.
Active Comparator: 2
High-dose treatment (200 FVIII u/kg per day).
Drug: Factor VIII concentrates
To be determined at the discretion of the investigator.
Other: High-dose treatment
200 FVIII u/kg per day.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
New York Presbyterian Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Manchester University NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2002

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2010

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 13, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 21, 2005

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ITI

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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