Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy on Systemic Lupus Erythematosus
February 10, 2012 updated by: Lai-Shan Tam, Chinese University of Hong Kong
Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy Restore Peripheral B Cell Abnormalities in Systemic Lupus Erythematosus(SLE)?
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Anticipated)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Hong Kong, China
- Department of Medicine and Therapeutics
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: 1
Rituximab
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Other Names:
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Active Comparator: 2
Rituximab + Cyclophosphamide
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Other Names:
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Active Comparator: 3
Cyclophosphamide
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
-Estimated glomerular filtration rate(FRR) of >90 mil/minute.1.73m2 -Urinary protein:urinary creatinine ratio of <0.2 -Inactive urinary sediment
Time Frame: wk48
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wk48
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Secondary Outcome Measures
Outcome Measure |
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
Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48
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baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2006
Primary Completion (Actual)
December 1, 2009
Study Completion (Actual)
December 1, 2009
Study Registration Dates
First Submitted
November 8, 2007
First Submitted That Met QC Criteria
November 8, 2007
First Posted (Estimate)
November 9, 2007
Study Record Updates
Last Update Posted (Estimate)
February 13, 2012
Last Update Submitted That Met QC Criteria
February 10, 2012
Last Verified
February 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SLE-2005-006
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.