Search / Trial NCT00001676

Cyclophosphamide and Fludarabine to Treat Lupus Nephritis

Launched by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) · Nov 3, 1999

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Trial Information

Current as of October 22, 2024

Completed

Keywords

Remission Renal Function Infection Germinal Center Immunoglobulin Glomerulonephritis Systemic Lupus Erythematosus Lupus Nephritis

Description

Studies at the NIH Clinical Center have shown that intermittent pulse cyclophosphamide therapy is effective for treating patients with severe lupus nephritis, but may result in substantial rates of sustained amenorrhea. Initial studies in patients with autoimmune rheumatic diseases have also suggested a beneficial effect from the lymphocyte-specific nucleoside analogs chlorodeoxyadenosine and fludarabine. Cyclophosphamide induces DNA cross-links whereas, nucleoside analogs inhibits DNA repair indicating complementary and partially synergistic modes of action. Whether combination of lower do...

Gender

ALL

Eligibility 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.

About National Institute Of Arthritis And Musculoskeletal And Skin Diseases (Niams)

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is a pivotal component of the National Institutes of Health (NIH) dedicated to advancing research and knowledge in the fields of arthritis, musculoskeletal disorders, and skin diseases. NIAMS sponsors a wide range of clinical trials aimed at improving the diagnosis, treatment, and prevention of these conditions. By fostering innovative research, collaborating with healthcare professionals, and engaging with patient communities, NIAMS strives to enhance the quality of life for individuals affected by these diseases, while promoting scientific discovery and public health initiatives.

Locations

Bethesda, Maryland, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Discussion 0