An Open Label Pilot Study Examining the Use of Rituximab in Patients With Wegener's Granulomatosis Who Have Experienced Disease Relapse on Standard Therapies

INCLUSION CRITERIA: Documentation of WG based on clinical characteristics and histopathologic and/or angiographic evidence of vasculitis. In the absence of histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the following criteria and in whom infectious and autoimmune diseases that may mimic WG have been excluded will also be eligible: A positive assay for anti-PR-3 or anti-MPO autoantibodies (ANCA) and the presence of glomerulonephritis defined by red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of immune deposits. A positive assay for anti-PR-3 or anti-MPO autoantibodies and at least 2 of the following: the presence of granulomatous inflammation on biopsy; abnormal chest radiograph (defined as the presence of nodules, fixed infiltrates, or cavities); nasal/oral inflammation on clinical examination. Age 18-75 years. Previous history of greater than or equal to 1 disease relapse as defined in Appendix I in patients fitting one of the below categories: Disease relapse occurred while receiving MTX or AZA for remission maintenance following remission induction with daily CYC according to standard regimens on which there has been published data Disease relapse occurred while on MTX following MTX induction according to the standard regimen on which there has been published data (98) in a patient who is unable to receive or is intolerant to daily CYC. Active WG within the past 12 months for which the patient received induction therapy with glucocorticoids combined with daily CYC or MTX according to standard regimens Evidence of current disease remission as defined in Appendix I and is currently receiving remission maintenance therapy consisting of MTX or AZA according to standard regimens. Patients may concurrently be receiving prednisone that is being tapered. Patients who completed their prednisone taper and are no longer receiving systemic glucocorticoids will be eligible if they are within 6 months of the time of prednisone discontinuation. Circulating ANCA as defined by the presence of antibodies detectable by indirect immunofluorescence performed by the NIH Clinical Immunology laboratory at a titer of greater than or equal to 1:40 on two determinations done at least 4 weeks apart. Patients who are historically ANCA positive and become ANCA negative during remission induction will be eligible if they again become positive to a level of greater than or equal to 1:40 on two determinations done at least 4 weeks apart at a prednisone dose of less than or equal to 50mg QOD or within 6 months following the discontinuation of prednisone. Willingness to travel to the NIH Willingness of both women and men to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception. EXCLUSION CRITERIA: Evidence of active infection, which, in the judgment of the investigator, is of greater danger to the patient than the underlying vasculitis. Patients who are pregnant or who are nursing infants will not be eligible. Women of childbearing potential must have a negative pregnancy test within one week prior to study entry. Serological evidence of infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen. A serological determination will be performed within two weeks of beginning study participation. Inability to comply with study guidelines. Hemocytopenia: platelet count greater than 80,000/mm(3), absolute neutrophil count less than 1500/mm(3), hematocrit less than 20% (in the absence of gastrointestinal bleeding or hemolytic anemia). Known allergy to murine proteins Use of illegal drugs or alcohol abuse (alcohol use that would prevent a patient from fulfilling the study requirements or that would increase the risk of study procedures.)