International Immune Tolerance Study

NCT00212472 | Terminated DMC

• 1 other identifier: ITI
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 39

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.

Conditions

Hemophilia A With Inhibitors

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• 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

Study Arms (2)

1

ACTIVE COMPARATOR

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

Drug: Factor VIII concentrates; Other: Low-dose treatment

2

ACTIVE COMPARATOR

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

Drug: Factor VIII concentrates; Other: High-dose treatment

Interventions

Factor VIII concentrates DRUG

To be determined at the discretion of the investigator.

1; 2

Low-dose treatment OTHER

50 FVIII u/kg three times a week.

1

High-dose treatment OTHER

200 FVIII u/kg per day.

2

Eligibility Criteria

• Age: Up to 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Presbyterian Hospital: lead
• Manchester University NHS Foundation Trust: collaborator

Study Sites (39)

University of Alabama Birmingham Medical Center

Birmingham, Alabama, 35233, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Mountain States Regional Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Rush Presbyterian St. Lukes

Chicago, Illinois, 60612, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Comprehensive Bleeding Disorders Center

Peoria, Illinois, 61614, United States

Location

Indiana Hemophilia & Thrombosis Center

Indianapolis, Indiana, 46034, United States

Location

Tulane University Hospital and Clinic

New Orleans, Louisiana, 70112, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

Location

Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health Hospitals

Ann Arbor, Michigan, 48109, United States

Location

MSU Centers for Bleeding & Clotting Disorders

East Lansing, Michigan, 48824, United States

Location

Children's Hospital Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Mayo Comprehensive Hemophilia Center

Rochester, Minnesota, 55905, United States

Location

Kansas City Regional Hemophilia Center-The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07102, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

Ted R. Montoya Hemophilia Treatment Center

Albuquerque, New Mexico, 87131, United States

Location

NY Presbyterian Hospital

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Christopher's Hospital for Children, Section of Hem/Onc

Philadelphia, Pennsylvania, 19134, United States

Location

The Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center

Houston, Texas, 77030, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507, United States

Location

Naval Medical Center

Portsmouth, Virginia, 23708, United States

Location

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, 53201, United States

Location

MeSH Terms

Interventions

Therapeutics

Study Officials

• Donna M DiMichele, MD

  Weill Cornell Medical College-NY Presybetrian Hospital

  PRINCIPAL INVESTIGATOR

• Charles Hay, MD

  Manchester Royal Infirmary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: July 1, 2002
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2012
• Last Updated: December 7, 2009

Record last verified: 2009-10

Locations

US (39)