Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy on Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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
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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.

Official Title
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Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy Restore Peripheral B Cell Abnormalities in Systemic Lupus Erythematosus(SLE)?

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Active proliferative lupus nephrites Biopsy confirmed active proliferative lupus nephritis within 3 months prior to enrollment Proteinuria >= 2g/day Active urinary sediments Activity index of >= 6 Elevated anti-double-stranded(anti-dsDNA) level at baseline Agreement to practice birth control SLE according to the American College of Rheumatology Criteria Informed consent was obtained Exclusion Criteria: Pre-existing renal failure History of cancer Human immunodeficiency virus infection Active hepatitis B or C infection Active tuberculosis Diabetes mellitus A ny other chronic disease Unwillingness to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Rituximab | Drug: rituximab<br>* 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.<br>* Other names: Mabthera;|
| Active Comparator: 2<br>Rituximab + Cyclophosphamide | Drug: rituximab<br>* 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.<br>* Other names: Mabthera;|
| Active Comparator: 3<br>Cyclophosphamide | Drug: rituximab<br>* 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.<br>* Other names: Mabthera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -Estimated glomerular filtration rate(FRR) of >90 mil/minute.1.73m2 -Urinary protein:urinary creatinine ratio of <0.2 -Inactive urinary sediment |  | wk48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -The estimated GFR,urinary protein values and urinary sediment -Changes in disease activity score(SLEDAI) -Other clinical features -Duration of B-cell depletion |  | baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Rituximab, Methylprednisolone, Cyclophosphamide