Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy on Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      This prospective randomized control trial is undertaken to evaluate the safety and efficacy
      of anti-CD20 monoclonal antibody, rituximab, used as 1. monotherapy, 2. in combination with
      cyclophosphamide, in the treatment of proliferative lupus nephritis, as compared with
      standard immunosuppressive therapy with cyclophosphamide and azathioprine.
    

Detailed description: 
      Twenty patients will be randomized into 3 treatment arms to receive:

        -  Rituximab of 1000 mg given 2 weeks apart. On day the of rituximab, and 'pulse'
           methylprednisolone 250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day
           5.

        -  A treatment dose rituximab of 1000mg given 2 weeks apart and 'pulse' methylprednisolone
           250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day 5, and 'pulse'
           cyclophosphamide 500mg/m2 at baseline and day 14.

        -  Sequential therapy with oral cyclophosphamide (50 to 100 mg/day) for 6 months followed
           by azathioprine (up to 2.5mg/kg/day) for maintenance up to 12 months. Oral prednisolone
           will be given at 0.5 mg/kg/day (up to 30 mg daily) for 4 weeks, tapered by 5 mg every 2
           weeks thereafter until 5mg /day for the rest of the study period. All patients would be
           started on angiotensin converting enzyme inhibitors before commencement of the trial and
           to continue at the same dosage throughout the study period. Patients who are on
           antimalarial agents and statins at baseline will be allowed to continue.

      Clinical examination and laboratory investigations will be performed at 0, 4, 8, 12, 24, 36
      and 48 weeks from the time of treatment. At each visit, patients will be evaluated for
      clinical manifestation of SLE and side effects of therapy. Laboratory parameters measured
      included the complete blood cell count with differential and platelet counts, chemistries
      survey, urinalysis, and 24- hour urinary for protein excretion and creatinine clearance.
    

Intervention name(s): rituximab
Intervention type(s): Drug
Intervention description(s): Rituximab of 1000 mg given 2 weeks apart. On day the of rituximab, and 'pulse' methylprednisolone 250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day 5.
A treatment dose rituximab of 1000mg given 2 weeks apart and 'pulse' methylprednisolone 250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day 5, and 'pulse' cyclophosphamide 500mg/m2 at baseline and day 14.
Sequential therapy with oral cyclophosphamide (50 to 100 mg/day) for 6 months followed by azathioprine (up to 2.5mg/kg/day) for maintenance up to 12 months. Oral prednisolone will be given at 0.5 mg/kg/day (up to 30 mg daily) for 4 weeks, tapered by 5 mg every 2 weeks thereafter until 5mg /day for the rest of the study period.
Other intervention name(s): Mabthera
Intervention MeSH terms: Rituximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: SLE; Rituximab; Methylprednisolone; Cyclophosphamide