High-Dose Intravenous (IV) Cyclophosphamide Versus Monthly IV Cyclophosphamide
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.
Lupus Erythematosus, Systemic
Drug: High-dose immunoablative therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Trial of High-Dose IV Cyclophosphamide Versus Monthly IV Cyclophosphamide|
- RIFLE [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2000|
|Study Completion Date:||April 2006|
|Primary Completion Date:||April 2006 (Final data collection date for primary outcome measure)|
Drug: High-dose immunoablative therapy
- High dose cyclophosphamide for 4 days.
- NIH monthly IV cytoxan for 6 months followed by quarterly for 2 years.
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.
|United States, Maryland|
|Johns Hopkins University Division of Rheumatology|
|Baltimore, Maryland, United States, 21205|
|United States, Pennsylvania|
|Drexel University School of Medicine, Division of Hematology/Oncology|
|Philadelphia, Pennsylvania, United States, 19102|
|United States, Wisconsin|
|Medical College of Wisconsin, Division of Rheumatology|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Michelle Petri, MD, MPH||Johns Hopkins University|