Hemophilia A With InhibitorsNCT00212472
International Immune Tolerance Study
A study testing Factor VIII concentrates, Low-dose treatment and High-dose treatment in people with Hemophilia A With Inhibitors, run by New York Presbyterian Hospital at 39 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 7 years
- Conditions the study is for
- Hemophilia A With Inhibitors
- What is being tested?
- Factor VIII concentrates, Low-dose treatment and High-dose treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 39 sitesUnited States
- Study dates
- Jul 2002to Dec 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- Age > 7 years at the start of ITI.
- Inability or unwillingness to comply with the protocol.
- Previous attempt at ITI.
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
United States39 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Ted R. Montoya Hemophilia Treatment Center
Albuquerque, New Mexico, 87131
University of Michigan Health Hospitals
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Mountain States Regional Hemophilia and Thrombosis Center
Aurora, Colorado, 80045
University of Alabama Birmingham Medical Center
Birmingham, Alabama, 35233
Tufts - New England Medical Center
Boston, Massachusetts, 02111
Children's Hospital Boston
Boston, Massachusetts, 02115
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Rush Presbyterian St. Lukes
Chicago, Illinois, 60612
Children's Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Columbus Children's Hospital
Columbus, Ohio, 43205
City of Hope Medical Center
Duarte, California, 91010
MSU Centers for Bleeding & Clotting Disorders
East Lansing, Michigan, 48824
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Texas Health Science Center-Gulf States Hemophilia & Thrombosis Center
Houston, Texas, 77030
Indiana Hemophilia & Thrombosis Center
Indianapolis, Indiana, 46034
Kansas City Regional Hemophilia Center-The Children's Mercy Hospital
Kansas City, Missouri, 64108
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Comprehensive Center for Bleeding Disorders
Milwaukee, Wisconsin, 53201
Children's Hospital Minneapolis
Minneapolis, Minnesota, 55404
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Tulane University Hospital and Clinic
New Orleans, Louisiana, 70112
NY Presbyterian Hospital
New York, New York, 10021
Mount Sinai Medical Center
New York, New York, 10029
Newark Beth Israel Medical Center
Newark, New Jersey, 07102
Saint Michael's Medical Center
Newark, New Jersey, 07102
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
Children's Hospital of Orange County
Orange, California, 92868
Comprehensive Bleeding Disorders Center
Peoria, Illinois, 61614
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
St. Christopher's Hospital for Children, Section of Hem/Onc
Philadelphia, Pennsylvania, 19134
The Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University
Portland, Oregon, 97239
Naval Medical Center
Portsmouth, Virginia, 23708
Mayo Comprehensive Hemophilia Center
Rochester, Minnesota, 55905
Maine Children's Cancer Program
Scarborough, Maine, 04074
All Children's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: 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.
Read the 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.
- Conditions
- Hemophilia A With Inhibitors
- Being tested
- Factor VIII concentrates, Low-dose treatment, High-dose treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Factor VIII concentratesDrug
To be determined at the discretion of the investigator.
Low-dose treatmentOther
50 FVIII u/kg three times a week.
High-dose treatmentOther
200 FVIII u/kg per day.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Low-dose treatment (50 FVIII u/kg three times a week). Receives: Drug: Factor VIII concentrates; Other: Low-dose treatment |
| 2 | Active comparator | High-dose treatment (200 FVIII u/kg per day). Receives: Drug: Factor VIII concentrates; Other: High-dose treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success-rate and partial success-rate
Measured: Up to 69 months
The time from the start of ITI to successful tolerance
Measured: Up to 33 months
The comparative cost-effectiveness of the two treatment arms
Measured: 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.
Measured: Up to 69 months
The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
Measured: Up to 45 months
Secondary outcomes (9)
The dose-regimen, success rate and time to ITI,
Measured: Up to 69 months
The starting inhibitor titre, success rate and time to ITI,
Measured: Up to 69 months
The peak historical inhibitor titre, success rate and time to ITI,
Measured: Up to 69 months
The peak inhibitor titre after starting ITI, success rate and time to success,
Measured: Up to 69 months
The age at the time of inhibitor detection, success-rate and time to success,
Measured: Up to 69 months
The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.
Measured: Up to 69 months
The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,
Measured: Up to 69 months
The effect of interim infections/immunisations, success rate and time to success,
Measured: Up to 69 months
The effect of treatment interruption, success rate and time to success.
Measured: Up to 69 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startJul 2002
- Primary completionDec 2010 (estimated)
- Study completionDec 2012 (estimated)
Why it stopped: The DSMB recommended stopping the study due to safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia A With InhibitorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York Presbyterian Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Manchester University NHS Foundation Trust
- Investigators
- Donna M DiMichele, MD, Principal investigator, Weill Cornell Medical College-NY Presybetrian HospitalCharles Hay, MD, Principal investigator, Manchester Royal Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00212472
- Sponsor's protocol ID
- ITI
- Status last verified
- Oct 2009
- First submitted
- 13 Sep 2005
- Last updated
- 7 Dec 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International Randomised Controlled Trial Of Immune Tolerance Induction
- ClinicalTrials.gov ID
- NCT00212472
- Acronym / sponsor ID
- ITI
- Conditions
- Hemophilia A With Inhibitors
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The DSMB recommended stopping the study due to safety concerns.
- Enrolment
- 134 participants (actual)
- Lead sponsor
- New York Presbyterian HospitalUniversity, hospital or other
- Collaborators
- Manchester University NHS Foundation Trust
- Study start
- Jul 2002
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Factor VIII concentrates, Other: Low-dose treatmentLow-dose treatment (50 FVIII u/kg three times a week). |
| 2 | Active comparator | Drug: Factor VIII concentrates, Other: High-dose treatmentHigh-dose treatment (200 FVIII u/kg per day). |
Who may qualify
- Ages
- Up to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Factor VIII concentratesTo be determined at the discretion of the investigator. | Drug | 1, 2 |
| Low-dose treatment50 FVIII u/kg three times a week. | Other | 1 |
| High-dose treatment200 FVIII u/kg per day. | Other | 2 |
Primary outcome
Success-rate and partial success-rate
Time frame: Up to 69 months
The time from the start of ITI to successful tolerance
Time frame: Up to 33 months
The comparative cost-effectiveness of the two treatment arms
Time frame: 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
The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
Time frame: Up to 45 months
9 secondary outcomes
The dose-regimen, success rate and time to ITI,
Time frame: Up to 69 months
The starting inhibitor titre, success rate and time to ITI,
Time frame: Up to 69 months
The peak historical inhibitor titre, success rate and time to ITI,
Time frame: Up to 69 months
The peak inhibitor titre after starting ITI, success rate and time to success,
Time frame: Up to 69 months
The age at the time of inhibitor detection, success-rate and time to success,
Time frame: 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
The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,
Time frame: Up to 69 months
The effect of interim infections/immunisations, success rate and time to success,
Time frame: Up to 69 months
The effect of treatment interruption, success rate and time to success.
Time frame: Up to 69 months
Results and safety
The study was stopped early (reason given: The DSMB recommended stopping the study due to safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donna M DiMichele, MD principal investigator
Weill Cornell Medical College-NY Presybetrian Hospital
Charles Hay, MD principal investigator
Manchester Royal Infirmary
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Factor VIII concentrates, Low-dose treatment and High-dose treatment in people with Hemophilia A With Inhibitors, run by New York Presbyterian Hospital at 39 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Dec 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The DSMB recommended stopping the study due to safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success-rate and partial success-rate (time frame: Up to 69 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2009.