High-Dose Intravenous (IV) Cyclophosphamide Versus Monthly IV Cyclophosphamide

NCT00005778 | Completed Phase 3

• 2 other identifiers: N01 AR92243NIAMS-046
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Lupus Erythematosus, Systemic

Keywords

Systemic Lupus Erythematosus (SLE); Cytoxan; Cyclophosphamide; High-dose immunoablative therapy

Outcome Measures

Primary Outcomes (1)

• RIFLE

  2.5 years

Interventions

High-dose immunoablative therapy DRUG

1. High dose cyclophosphamide for 4 days. 2. NIH monthly IV cytoxan for 6 months followed by quarterly for 2 years.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

All patients with moderate-to-severe SLE will be considered for this trial, including women and minorities. SLE is too rare a disease in children for it to be feasible to include them. Patients must meet the following criteria to be eligible for participation in this clinical trial: * Four or more ACR criteria (90), as revised by Hochberg (91) for the classification of SLE. * Involvement of one or more of the following organ systems (renal, neurologic, hematologic, cardiac, pulmonary, cutaneous, gastrointestinal) of moderate-to-severe severity as indicated by an "A" score on the BILAG, a "2" or "3" for severity on SLAM, or severe enough to require hospitalization if the organ involvement was not "captured" on either the BILAG or SLAM instruments. * A lack of response to daily corticosteroids in moderate-to-high doses (0.5 -1 mg prednisone/kg/day or equivalent anti-inflammatory dose of methyprednisolone, dexamethasone, or triamicinolone). When cyclophosphamide is the accepted standard of care (renal and neurologic), the maximally tolerated dose of prednisone will be sufficient to meet the corticosteroid criterion. The ideal body weight will be used for this criterion in patients who are morbidly obese. The equivalent dose of triamcinolone (4mg triamcinolone=5mg prednisone) can be used to meet the criterion. And/or: * A lack of response to IV pulse corticosteroids (1 gram methylprednisolone or 180 mg dexamethasone). * Duration of treatment to determine lack of response is 3 days or longer for neurologic, renal, hematologic, pulmonary, or cardiac lupus, one month or longer for serositis. And/or: * Equivalent degree of immunosuppression with azathioprine, methotrexate, cyclosporin, or mycophenolate mofetil. Equivalent degrees of immunosuppression are: azathioprine - 100 mg daily or more; methotrexate - 7.5 mg weekly or more; cyclosporin - 150 mg daily or more; mycophenolate mofetil - 1000 mg daily or more. Duration to determine lack of response should be one month or longer. And/or: * Appropriate other treatment (such as intravenous immunoglobulin for hemolytic anemia and thrombocytopenia). * SLE patients seeking treatment for neurological complaints will be evaluated by a neurologist to concur that the patient meets eligibility criteria. * Appropriate other treatment for cutaneous lupus patients may include combination antimalarial drugs (such as the combination of hydroxychloroquine or chloroquine with quinacrine). * Patients may enter the trial if they received one dose of IV cyclophosphamide to "temporize" or "stablize" them prior to screening visit or after signing consent or if previous IV cyclophosphamide was for a PAST organ system, and patient presents with NEW organ system requiring IV cyclophosphamide. * Insurance or other source of funds to pay for expenses related to this trial. Exlcusion Criteria: * Age less than 18 years and over 70 years. * Any risk of pregnancy - ALL female patients must have an effective means of birth control or be infertile due to hysterectomy, fallopian tube surgery, or menopause. * Previous completion of the NIH IV cyclophosphamide protocol. * Cardiac ejection fraction \< 45%. * Serum creatinine \> 3.0 mg/dL. * FVC or FEV \< 50% predicted. * Bilirubin \> 2.0, transaminases \> 2x normal. * Patients who are preterminal or moribund. * SLE patients presenting with arthritis for entry organ system.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (3)

Johns Hopkins University Division of Rheumatology

Baltimore, Maryland, 21205, United States

Location

Drexel University School of Medicine, Division of Hematology/Oncology

Philadelphia, Pennsylvania, 19102, United States

Location

Medical College of Wisconsin, Division of Rheumatology

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (6)

• Brodsky RA, Petri M, Smith BD, Seifter EJ, Spivak JL, Styler M, Dang CV, Brodsky I, Jones RJ. Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease. Ann Intern Med. 1998 Dec 15;129(12):1031-5. doi: 10.7326/0003-4819-129-12-199812150-00007.

  PMID: 9867758 BACKGROUND

• Brodsky RA, Sensenbrenner LL, Jones RJ. Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation. Blood. 1996 Jan 15;87(2):491-4.

  PMID: 8555470 BACKGROUND

• Brodsky RA, Smith BD. Bone marrow transplantation for autoimmune diseases. Curr Opin Oncol. 1999 Mar;11(2):83-6. doi: 10.1097/00001622-199903000-00002.

  PMID: 10188071 BACKGROUND

• Levite M, Zinger H, Zisman E, Reisner Y, Mozes E. Beneficial effects of bone marrow transplantation on the serological manifestations and kidney pathology of experimental systemic lupus erythematosus. Cell Immunol. 1995 Apr 15;162(1):138-45. doi: 10.1006/cimm.1995.1061.

  PMID: 7704902 BACKGROUND

• Petri M, Jones RJ, Brodsky RA. High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum. 2003 Jan;48(1):166-73. doi: 10.1002/art.10752.

  PMID: 12528116 BACKGROUND

• Petri M. Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus. 2004;13(5):366-71. doi: 10.1191/0961203303lu1028oa.

  PMID: 15230294 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Michelle Petri, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 3, 2000
• First Posted: June 5, 2000
• Study Start: January 1, 2000
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: November 6, 2008

Record last verified: 2008-11

Locations

US (3)