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International Immune Tolerance Study

Primary Purpose

Hemophilia A With Inhibitors

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Factor VIII concentrates
Low-dose treatment
High-dose treatment
Sponsored by
New York Presbyterian Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A With Inhibitors

Eligibility Criteria

undefined - 7 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama Birmingham Medical Center
  • City of Hope Medical Center
  • Children's Hospital of Orange County
  • Mountain States Regional Hemophilia and Thrombosis Center
  • All Children's Hospital
  • Children's Healthcare of Atlanta
  • Rush Presbyterian St. Lukes
  • Children's Memorial Hospital
  • Comprehensive Bleeding Disorders Center
  • Indiana Hemophilia & Thrombosis Center
  • Tulane University Hospital and Clinic
  • Maine Children's Cancer Program
  • Tufts - New England Medical Center
  • Children's Hospital Boston
  • University of Michigan Health Hospitals
  • MSU Centers for Bleeding & Clotting Disorders
  • Children's Hospital Minneapolis
  • Mayo Comprehensive Hemophilia Center
  • Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
  • Hackensack University Medical Center
  • Newark Beth Israel Medical Center
  • Saint Michael's Medical Center
  • Ted R. Montoya Hemophilia Treatment Center
  • NY Presbyterian Hospital
  • Mount Sinai Medical Center
  • University of North Carolina at Chapel Hill
  • Children's Hospital Medical Center of Akron
  • Cincinnati Children's Hospital Medical Center
  • Columbus Children's Hospital
  • Oregon Health and Science University
  • Children's Hospital of Philadelphia
  • St. Christopher's Hospital for Children, Section of Hem/Onc
  • The Hemophilia Center of Western Pennsylvania
  • St. Jude Children's Research Hospital
  • Vanderbilt University Medical Center
  • University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
  • Children's Hospital of the King's Daughters
  • Naval Medical Center
  • Comprehensive Center for Bleeding Disorders

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Low-dose treatment (50 FVIII u/kg three times a week).

High-dose treatment (200 FVIII u/kg per day).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 13, 2005
Last Updated
December 4, 2009
Sponsor
New York Presbyterian Hospital
Collaborators
Manchester University NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT00212472
Brief Title
International Immune Tolerance Study
Official Title
An International Randomised Controlled Trial Of Immune Tolerance Induction
Study Type
Interventional

2. Study Status

Record Verification Date
October 2009
Overall Recruitment Status
Terminated
Why Stopped
The DSMB recommended stopping the study due to safety concerns.
Study Start Date
July 2002 (undefined)
Primary Completion Date
December 2010 (Anticipated)
Study Completion Date
December 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
New York Presbyterian Hospital
Collaborators
Manchester University NHS Foundation Trust

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A With Inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Low-dose treatment (50 FVIII u/kg three times a week).
Arm Title
2
Arm Type
Active Comparator
Arm Description
High-dose treatment (200 FVIII u/kg per day).
Intervention Type
Drug
Intervention Name(s)
Factor VIII concentrates
Intervention Description
To be determined at the discretion of the investigator.
Intervention Type
Other
Intervention Name(s)
Low-dose treatment
Intervention Description
50 FVIII u/kg three times a week.
Intervention Type
Other
Intervention Name(s)
High-dose treatment
Intervention Description
200 FVIII u/kg per day.
Primary Outcome Measure Information:
Title
Success-rate and partial success-rate
Time Frame
Up to 69 months
Title
The time from the start of ITI to successful tolerance
Time Frame
Up to 33 months
Title
The comparative cost-effectiveness of the two treatment arms
Time Frame
Up to 69 months
Title
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
Title
The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
Time Frame
Up to 45 months
Secondary Outcome Measure Information:
Title
The dose-regimen, success rate and time to ITI,
Time Frame
Up to 69 months
Title
The starting inhibitor titre, success rate and time to ITI,
Time Frame
Up to 69 months
Title
The peak historical inhibitor titre, success rate and time to ITI,
Time Frame
Up to 69 months
Title
The peak inhibitor titre after starting ITI, success rate and time to success,
Time Frame
Up to 69 months
Title
The age at the time of inhibitor detection, success-rate and time to success,
Time Frame
Up to 69 months
Title
The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.
Time Frame
Up to 69 months
Title
The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,
Time Frame
Up to 69 months
Title
The effect of interim infections/immunisations, success rate and time to success,
Time Frame
Up to 69 months
Title
The effect of treatment interruption, success rate and time to success.
Time Frame
Up to 69 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donna M DiMichele, MD
Organizational Affiliation
Weill Cornell Medical College-NY Presybetrian Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Charles Hay, MD
Organizational Affiliation
Manchester Royal Infirmary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Birmingham Medical Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Mountain States Regional Hemophilia and Thrombosis Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
All Children's Hospital
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush Presbyterian St. Lukes
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Comprehensive Bleeding Disorders Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61614
Country
United States
Facility Name
Indiana Hemophilia & Thrombosis Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46034
Country
United States
Facility Name
Tulane University Hospital and Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Maine Children's Cancer Program
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Tufts - New England Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Health Hospitals
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
MSU Centers for Bleeding & Clotting Disorders
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
Children's Hospital Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Mayo Comprehensive Hemophilia Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Newark Beth Israel Medical Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Facility Name
Saint Michael's Medical Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Facility Name
Ted R. Montoya Hemophilia Treatment Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
NY Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Children's Hospital Medical Center of Akron
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Columbus Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
St. Christopher's Hospital for Children, Section of Hem/Onc
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134
Country
United States
Facility Name
The Hemophilia Center of Western Pennsylvania
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Naval Medical Center
City
Portsmouth
State/Province
Virginia
ZIP/Postal Code
23708
Country
United States
Facility Name
Comprehensive Center for Bleeding Disorders
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

International Immune Tolerance Study

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