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

Inclusion Criteria

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.