Combination of Cyclophosphamide and Fludarabine for Lupus Nephritis: Tolerance, Toxicity, Efficacy and Effects on B and T Lymphocyte Regeneration

Study start date: January 1, 1998

Patients must be 18 years of age or older and able to provide informed consent. Patients must have at least 4 criteria for SLE as defined by the American Rheumatism Association (ARA). Active glomerulonephritis with: Renal biopsy within 1 year with class III or class IV active lupus nephritis, AND; Abnormal urine analysis: Greater than 10 RBC/hpf and cellular (RBC, WBC or mixed) casts, OR; Greater than 10 RBC/hpf and proteinuria greater than 2 g/day, OR; Proteinuria greater than 3.5 g/day. No patients with severe proliferative lupus nephritis: a. very active renal histology with crescents or necrosis in more than 25% of glomeruli; or b. rapidly progressive glomerulonephritis (doubling of serum creatinine in less than or equal to 3 months); or c. severe impairment of renal function Cr greater than 2.5 mg/dL or GFR less than 50 mL/min measured by inulin clearance. Patient has not had previous immunosuppressive therapy: Patients must not be receiving azathioprine, cyclosporine, methotrexate. Patients receiving these drugs will be eligible only if these drugs are discontinued and after a waiting period of greater than or equal to 4 weeks; Patients must not be receiving cyclophosphamide: Greater than 3 pulses (maximum 1 g/m(2)/pulse) within the last 12 months or since last renal biopsy showing active disease; OR greater than 6 pulses ever. Patients must not have had pulse therapy with glucocorticoids or any experimental therapy during the 4 weeks before study entry. Patients who need at study entry oral corticosteroids in dosages greater than 0.5 mg/kg/day of predisone to control extrarenal disease are not eligible. Patients with active or chronic infection are not eligible. Patients who are pregnant, breast-feeding or using inadequate birth control are not eligible. Patients who have poorly controlled diabetes mellitus or with evidence of end-organ damage are not eligible. No history of cerebrovascular accident, seizures within the last 5 years or chronic neurologic disease. No history of malignancy other than squamous cell and/or basal carcinoma of the skin. No confounding medical illness that in the judgment of investigators would pose added risk for study participants such as: Unstable coronary artery disease, cardiomyopathy or dysrhythmia requiring therapy; Pulmonary disease (PFTs less 70% of predicted value or DLCO less than 60%), or; Hematologic disease (Hb less than 8 mg/dL, platelets less than 100,000 micro liters or WBC less than 2,500/micro liters.