A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN.

The authors present and discuss a new protocol for active multiple sclerosis (MS) patients. A double blind randomized controlled multicenter study was planned to study the effects of a combination regimen therapy: cyclophosphamide plus beta interferon versus beta interferon alone on both relapsing-remitting and secondary MS patients with active disease. The primary endpoint of this study is the number of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy, number of patients who were relapse-free, number of patients who improved, yearly relapses, quality of life, disability and cognitive impairment, frequency of neutralizing antibodies, safety of the combination therapy (cyclophosphamide + beta interferon). The study will enroll 225 patients in 25 Italian MS centers. Eligible for the study are patients with either relapsing-remitting or secondary MS according McDonald criteria on 6-24 months beta interferon treatment with active disease (new gadolinium enhancing lesion or who experienced a new relapse on beta interferon treatment). Clinical evaluation will be performed every 4 months, MRI yearly. Vital signs and eventual adverse events will be collected monthly. The study will last 36 months, 12 for the enrollment phase and 24 for the treatment phase. The study will start on April 2004.