Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A
This study has been terminated.
(Sponsor no longer funding study.)
Information provided by (Responsible Party):
Craig Kessler, Georgetown University
First received: March 23, 2006
Last updated: January 9, 2014
Last verified: January 2014
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.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- 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. ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||January 2011 (Final data collection date for primary outcome measure)
Patients will recieve rituximab.
Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies
Other Name: Rituximab
Other Name: corticosteriods
Active Comparator: Oral cyclophosphamide
Patients will receive oral cyclophosphamide.
Other Name: corticosteriods
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.
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- 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, immodulatory, 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00306670
||Craig Kessler, MD
||Georgetown University Hospital
No publications provided
||Craig Kessler, Professor, Georgetown University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 23, 2006
||January 9, 2014
||United States: Food and Drug Administration
Keywords provided by Georgetown University:
Acquired Hemophilia A
Anti-Factor VIII antibodies
Anti-Factor VIII inhibitors
Factor VIII inhibitors
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 01, 2015
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs