Clinical trial NCT00212472: International Immune Tolerance Study
Official title: An International Randomised Controlled Trial Of Immune Tolerance Induction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hemophilia A With Inhibitors
Lead sponsor: New York Presbyterian Hospital
Sponsor class: OTHER
Collaborators: name: Manchester University NHS Foundation Trust
First posted: 2005-09-21
Enrollment: 134
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Success-rate and partial success-rate
timeFrame: Up to 69 months
measure: The time from the start of ITI to successful tolerance
timeFrame: Up to 33 months
measure: The comparative cost-effectiveness of the two treatment arms
timeFrame: Up to 69 months
measure: A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days.
timeFrame: Up to 69 months
measure: The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
timeFrame: Up to 45 months
Secondary outcomes:
measure: The dose-regimen, success rate and time to ITI,
timeFrame: Up to 69 months
measure: The starting inhibitor titre, success rate and time to ITI,
timeFrame: Up to 69 months
measure: The peak historical inhibitor titre, success rate and time to ITI,
timeFrame: Up to 69 months
measure: The peak inhibitor titre after starting ITI, success rate and time to success,
timeFrame: Up to 69 months
measure: The age at the time of inhibitor detection, success-rate and time to success,
timeFrame: Up to 69 months
measure: The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.
timeFrame: Up to 69 months
measure: The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,
timeFrame: Up to 69 months
measure: The effect of interim infections/immunisations, success rate and time to success,
timeFrame: Up to 69 months
measure: The effect of treatment interruption, success rate and time to success.
timeFrame: Up to 69 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham Medical Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Mountain States Regional Hemophilia and Thrombosis Center
state: Colorado
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Rush Presbyterian St. Lukes
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Comprehensive Bleeding Disorders Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center
state: Indiana
city: New Orleans
country: United States
facility: Tulane University Hospital and Clinic
state: Louisiana
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Boston
country: United States
facility: Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Hospitals
state: Michigan
city: East Lansing
country: United States
facility: MSU Centers for Bleeding & Clotting Disorders
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospital Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Mayo Comprehensive Hemophilia Center
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Ted R. Montoya Hemophilia Treatment Center
state: New Mexico
city: New York
country: United States
facility: NY Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children, Section of Hem/Onc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: The Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center
state: Virginia
city: Milwaukee
country: United States
facility: Comprehensive Center for Bleeding Disorders
state: Wisconsin
Study officials:
affiliation: Weill Cornell Medical College-NY Presybetrian Hospital
name: Donna M DiMichele, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Manchester Royal Infirmary
name: Charles Hay, MD
role: PRINCIPAL_INVESTIGATOR
References: