Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis
Condition: Multiple Sclerosis (MS)
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine if a sequential combination therapy of natalizumab
      and alemtuzumab induces peripheral tolerance and reduces the annualized relapse rate (ARR) in
      patients with relapsing-remitting multiple sclerosis (RRMS).
    

Detailed description: 
      To determine if treatment with alemtuzumab after natalizumab reduces the ARR in patients with
      RRMS. The goal of this trial is to establish a disease-free state over a 24 months period in
      patients who received the natalizumab-alemtuzumab sequential therapy. The target population
      for this study are RRMS patients nearing the end of their natalizumab treatment
      regimen.Participants will be recruited from four different sites. Patients who meet all
      inclusion/exclusion criteria will be eligible for enrollment in the study.

      Alemtuzumab (Lemtrada®) will be administered at a dose of 12 mg/d by intravenous (i.v.)
      infusion every day for five consecutive days within 14 days of the last dose of natalizumab.
      After 12 months, patients will be treated with a second course of alemtuzumab 12 mg/d by
      intravenous (i.v.) infusion every day for three consecutive days, and participants will be
      followed open-label for another 12 months per standard of care. Outside the scope of this
      study, the intention is to follow all study participants in participating centers long-term,
      and to record disease activity and treatment response.

      Natalizumab treatment sequesters leukocytes out of the central nervous system (CNS) into the
      peripheral blood. Immediate sequential alemtuzumab therapy will deplete these cells more
      completely than alemtuzumab monotherapy, and prevent reactivation of disease activity
      previously treated with natalizumab. Thus, investigators hypothesize that sequential
      natalizumab - alemtuzumab therapy will prevent disease activation after cessation of
      natalizumab, and will provide sustained disease remission in many patients.

      Clinical follow up by the treating physician will occur at months 0, 3, 6, 9, 12, 18 and 24
      or immediately following clinical exacerbations months. During clinical visits, comprehensive
      medical history data will be obtained by the treating physician. Clinical visits due to
      suspected exacerbations associated with CNS (central nervous system) demyelination, and
      associated diagnostic studies and treatments, will be covered under the medical standard of
      care by third party payers. A recommendation to reevaluate the patient within 3 months
      following the clinical event to assess for extent of recovery will be made.

      Standardized MRI studies of the brain will be performed at 0, 6, 12 and 24 months. Clinical
      imaging studies of the brain will be performed during or immediately following the onset of a
      clinical exacerbation will be performed at the discretion of the site PI with scan costs
      covered under the medical standard of care. An end of study clinical MRI of the brain with
      and without contrast will be recommended to study participants at week 96 as medical standard
      of care.
    

Intervention name(s): Alemtuzumab
Intervention type(s): Drug
Intervention description(s): Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Other intervention name(s): Lemtrada
Intervention MeSH terms: Alemtuzumab
Intervention model: Single Group Assignment
Intervention model description: To determine if treatment with alemtuzumab after natalizumab maintains or reduces the ARR in patients with RRMS. The goal of this trial is to establish a disease-free state over a 24 months period in patients who received the natalizumab-alemtuzumab sequential therapy.
Masking: None (Open Label)
Primary purpose: Treatment