High-Dose Intravenous (IV) Cyclophosphamide Versus Monthly IV Cyclophosphamide
Condition: Lupus Erythematosus, Systemic
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 3

Summary: 
      This study compares the effectiveness of high-dose cyclophosphamide treatment with the "gold
      standard" treatment, monthly intravenous (IV) cyclophosphamide, in people with moderate to
      severe lupus that does not respond to high-dose corticosteroid therapy. We will give patients
      either IV cyclophosphamide (750 milligrams per square meter of body surface area) monthly for
      6 months, followed by quarterly maintenance therapy, or high-dose IV cyclophosphamide (50
      milligrams per kilogram body weight per day) for the first four days of the study. Patients
      will be followed for 24 months after therapy.
    

Detailed description: 
      Systemic lupus erythematosus (SLE or lupus) remains the prototypic autoimmune disease. Recent
      data show that its incidence has tripled since 1970 and its prevalence is 1 in 800 in
      Rochester, Minnesota. The natural history of lupus in our cohort is one of (1) relapsing/
      remitting or (2) chronic activity, with only 17 percent of patients having periods of long
      quiescence. Over 75 percent of our African-American patients and 50 percent of our Caucasian
      patients have renal (kidney) involvement. Over 50 percent suffer permanent damage in one or
      more organ systems, and over 15 percent have renal failure.

      Researchers at the National Institutes of Health (NIH) have shown that, for patients with
      severe lupus, especially with renal involvement, monthly IV pulse cyclophosphamide (500 to
      1000 mg/m squared BSA) for 6 months followed by quarterly maintenance for 2 years is superior
      to high-dose corticosteroid treatment. NIH and others have shown that IV pulse
      cyclophosphamide is also effective for severe lupus in other organs. However, even monthly IV
      cyclophosphamide is not successful in all cases, and it, too, has associated toxicity,
      especially premature ovarian failure. For that reason, we have pioneered the use of high-dose
      immunoablative cyclophosphamide (200 mg/kg) in 10 patients with severe lupus refractory to
      other treatments.

      Because of the initial success of this approach, including 75 percent complete response (on
      no medications) in renal lupus, we are conducting a controlled trial of high-dose
      immunoablative cyclophosphamide versus the "gold standard" monthly IV cyclophosphamide in
      people with moderate to severe lupus refractory to high-dose corticosteroid therapy. We will
      give patients either 750 mg/m2 of body surface area IV cyclophosphamide monthly for 6 months,
      followed by quarterly maintenance therapy (we will readmit patients, if necessary, for
      infections or other complications) or cyclophosphamide 50 mg/kg/d intravenously on days 1-4.
      We will calculate the dose of cyclophosphamide according to ideal body weight. Patients are
      scheduled to receive only one course of therapy. We will follow patients according to the
      infective guidelines for BMT.
    

Intervention name(s): High-dose immunoablative therapy
Intervention type(s): Drug
Intervention description(s): High dose cyclophosphamide for 4 days.
NIH monthly IV cytoxan for 6 months followed by quarterly for 2 years.
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Systemic Lupus Erythematosus (SLE); Cytoxan; Cyclophosphamide; High-dose immunoablative therapy