An Open Label Pilot Study Examining the Use of Rituximab in Patients With Wegener's Granulomatosis Who Have Experienced Disease Relapse on Standard Therapies
Data Collection
Autoimmune Diseases+11
+ Cardiovascular Diseases
+ Immune System Diseases
Treatment Study
Summary
Study start date: October 1, 2003
Actual date on which the first participant was enrolled.This pilot study will seek to investigate the use of rituximab in patients with Wegener's granulomatosis who have experienced disease relapse through standard therapies. Rituximab is a chimeric monoclonal antibody directed against CD20, which induces B cell death and results in rapid and sustained depletion of circulating and tissue-based B cells. The objectives of this protocol will be to establish the safety of rituximab in Wegener's granulomatosis, to examine the ability of rituximab to reduce the level of circulating antineutrophil cytoplasmic antibodies (ANCA), and to preliminarily explore whether rituximab is able to prevent disease relapse. This prospective standardized open label trial will enroll 10 patients who have a well-documented history of disease relapse while receiving immunosuppressive therapy given according to published regimens and who are ANCA positive after remission induction. Patients will be enrolled once they have achieved remission from a recent relapse and are receiving either methotrexate or azathioprine for remission maintenance. All patients will receive rituximab 375 mg/M(2) once a week for 4 weeks. During and following the rituximab treatment period, patients will remain on their remission maintenance agent of methotrexate or azathioprine. Patients who are enrolled while on prednisone will continue to taper the dosage to discontinuation as medically permitted. Following the 4 weekly infusions of rituximab, patients will be followed prospectively for evidence of effective B cell depletion, features of drug toxicity, level of circulating ANCA, and clinical disease status. Patients whose ANCA levels become undetectable following the infusion of rituximab may be retreated with a second 4 week course of rituximab should their ANCA titer become positive (greater than or equal to 1:40) and there has been a return of B cells in the peripheral blood. Methotrexate or azathioprine will be continued for two years past remission, after which time, this will be tapered and discontinued. Patients will continue to be monitored for two years off all immunosuppressive therapy or if a disease relapse should occur, for a minimum of 12 months after the last rituximab infusion.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.10 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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.)
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOpen National Institute of Allergy and Infectious Diseases (NIAID) in Google Maps