- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00306670
Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A
December 20, 2016 updated by: Craig Kessler, Georgetown University
A Prospective, Phase II/III Randomized, Mult-institutional Controlled, Open-label, Phase II Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Patients With Acquired Hemophilia A
The purpose of this study is to evaluate the rate of response when administering rituximab to suppress or eliminate the anti-body in a patient's blood that inhibits the effectiveness of their factor replacement product compared to treatment using cyclophosphamide.
This is a Phase 2/3 study to find out what effects (good and bad) and response rituximab has on a patient and their anti-Factor VIII antibodies.
Also, to compare the effect (good and bad) of the rituximab with cyclophosphamide on a patient and their anti-Factor VIII antibodies to see which is better.
This research is being done because we do not know which treatment regimen (rituximab or cyclophosphamide) is more effective in eliminating or suppressing the anti-Factor VIII antibody in patients with acquired Hemophilia A.
Study Overview
Detailed Description
This is a prospective Phase II randomized multi-institutional controlled pilot trial comparing the regimen of single agent rituximab with 6 weeks cytotoxic therapy with oral cyclophosphamide to eradicate or suppress autoimmune anti-factor VIII antibodies in individuals with acquired hemophilia A. Patients will be randomized to receive either of these two regimens when their autoimmune anti-factor VIII antibodies prove to be refractory to initial upfront immunosuppressive treatment with oral prednisone 1 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks.
Patients will be randomized to the treatment cohorts according to the biostatistical methods.
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Phase 2
- Phase 3
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
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosis of acquired hemophilia A in a previously non-coagulopathic individual.
- Prior treatment with at least 3 weeks of immunosuppressive therapy
- Factor VIII: C levels <50% within 14 days prior to study entry, which do not correct in coagulation assays in which normal plasma is mixed and incubated with patient plasma.
- Measurable anti-factor VIII:C antibody inhibitor activity > 0.6 Bethesda Units/ml.
- Age ³18 years
- Written informed consent
- Use of an effective means to avoid pregnancy, including abstinence, for women of childbearing potential,.
- Serum bilirubin less than or equal to the upper limit of normal (ULN); ALT and AST £2.5´ ULN within 14 days prior to study entry
- Serum creatinine £1.5´ the ULN within 14 days prior to study entry
- Negative serum pregnancy test, for all women of childbearing potential, within 14 days prior to study entry
Exclusion Criteria:
- Continued treatment requirement of prednisone ≥30mg/day or equivalent dosing of other corticosteroid preparations to control serious symptoms of an underlying autoimmune disease state.
- Treatment with cyclophosphamide, danazol, vinca alkaloids, azathioprine, IVIG, or other immunosuppressive, immunomodulatory, or cytotoxic agents (other than decreasing doses of corticosteroids) within 30 days prior to study entry.
- Anticipated need for repeated extracorporeal plasmapheresis in order to reverse refractory bleeding associated with acquired hemophilia.
- Treatment with other experimental agents within 30 days prior to study entry
- Known sensitivity to murine or chimeric products
- Hepatitis BsAg positivity or high risk for reactivation of Hepatitis B.
- Active infection requiring antibiotic therapy within 7 days prior to study entry
- Current use of any required medications, which in the opinion of the treating physician, could be inducing the formation of auto-FVIII:C inhibitory antibodies
- Prior treatment with rituximab or other monoclonal antibody therapy
- Known HIV antibody positivity
- NCI-CTC Grade ³1 cardiac arrhythmia ( refer to CTC v3)
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Currently pregnant women, lactating women, or women within 12 months of delivery, spontaneous miscarriage, or therapeutic or elective termination of pregnancy.
- Known severe leucopenia (absolute neutrophil count <1000/µL) or thrombocytopenia (<25,000/µL);
- Known pre-existing cystitis or severe urinary outflow obstruction.
- Known history of recurrent severe opportunistic infections, eg. generalized herpes zoster;
- Inability or unwillingness to comply with study design and requirements and follow-up procedures.
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 |
Intervention / Treatment |
---|---|
Experimental: Rituximab
Patients will receive rituximab.
|
Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies
Other Names:
<30 mg/day
Other Names:
|
Active Comparator: Oral cyclophosphamide
Patients will receive oral cyclophosphamide.
|
<30 mg/day
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody.
Time Frame: When 25 patients have completed the study.
|
the 2 recruited patients did not eradicate their inhibitors with 3 weeks of corticosteroids and did not progress in clinical trial since funding was eliminated and study terminated
|
When 25 patients have completed the study.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Craig Kessler, MD, Georgetown University Hospital
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
April 1, 2006
Primary Completion (Actual)
January 1, 2011
Study Completion (Actual)
August 1, 2011
Study Registration Dates
First Submitted
March 23, 2006
First Submitted That Met QC Criteria
March 23, 2006
First Posted (Estimate)
March 24, 2006
Study Record Updates
Last Update Posted (Actual)
February 10, 2017
Last Update Submitted That Met QC Criteria
December 20, 2016
Last Verified
December 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Hematologic Diseases
- Blood Coagulation Disorders, Inherited
- Coagulation Protein Disorders
- Hemorrhagic Disorders
- Genetic Diseases, Inborn
- Blood Coagulation Disorders
- Hemophilia A
- Physiological Effects of Drugs
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Immunological
- Rituximab
- Prednisone
Other Study ID Numbers
- U2688
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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