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.
• 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