Rituximab to Treat Severe Hemophilia A
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Rituximab
Intervention description: Rituximab by slow intravenous infusion; for participants greater than or equal to 10 kg, 375 mg per m^2 BSA weekly for 4 weeks; for participants less than 10 kg, 12.5 mg/kg weekly for 4 weeks
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Months
Healthy volunteers: No
Keywords: Blood Coagulation Factor Inhibitors

Summary:

      Hemophilia A is a serious blood clotting disorder caused by a lack of factor VIII, a
      specialized protein needed for normal blood clotting to occur. Individuals with this disease
      may experience spontaneous bleeding, pain and swelling in their joints due to excess
      bleeding, and bruising. A common treatment for severe hemophilia A is to intravenously
      replace the deficient blood clotting factor; however, some individuals may develop antibodies
      to this replacement factor. This study will evaluate the effectiveness of rituximab at
      reducing the antibodies that develop in response to the replacement factor in individuals
      with severe hemophilia A.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Severe congenital hemophilia A

          -  Documented historical inhibitor titer to factor VIII of at least 5 BU/mL

          -  Inhibitor level greater than or equal to 5 BU/mL 5 to 14 days after initial factor
             VIII exposure during screening

        Exclusion Criteria:

          -  Known hypersensitivities or allergies to murine and/or humanized antibodies

          -  Currently participating in investigational hemophilia studies

          -  HIV infected

          -  Any immunodeficiency disorder

          -  Liver disease and serum ALT or AST is greater than three times the upper limit of
             normal, albumin is less than 2.5g/dl, and/or INR is greater than 1.7

          -  Received interferon or other immunomodulatory drugs, such as steroids or cytotoxic
             therapy in the 30 days prior to study entry

          -  History of cardiac arrhythmias, any active febrile illness, kidney insufficiency, or
             pulmonary infiltrates

          -  Has previously received rituximab treatment

          -  Currently undergoing immune tolerance therapy

          -  Evidence of Hepatitis B (HBV) infection, defined as one of the following:

               -  HBsAg positive

               -  HBsAg negative, HBsAb negative, HBcAb positive, and HBV DNA positive

          -  Participants with a high responding inhibitor (at least 5 BU/mL) first detected fewer
             than 12 months prior to study entry, unless the participant has failed immune
             tolerance therapy, defined as one of the following:

               1. Failure to fulfill the criteria for full or partial success within 33 months, as
                  defined by a factor VIII recovery greater than or equal to 66% of expected and
                  half-life greater than or equal to 6 hours measured after a 72-hour
                  treatment-free washout period

               2. Failure to achieve greater than 20% reduction in inhibitor titer during each
                  interim non-overlapping 6-month period of ITT in the absence of documented
                  infection, with 9 months as the minimum treatment period and 33 months as the
                  maximum possible duration of unsuccessful ITT

               3. Withdrawal from ITT for any other reason

          -  Routinely receive factor VIII concentrate for the treatment of both major and minor
             bleeding events

          -  Has received factor VIII concentrate in the 7 days prior to study entry