Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lai-Shan Tam, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT00556192
First received: November 8, 2007
Last updated: February 10, 2012
Last verified: February 2012

November 8, 2007
February 10, 2012
June 2006
December 2009   (final data collection date for primary outcome measure)
-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 ] [ Designated as safety issue: Yes ]
  • Estimated glomerular filtration rate(FRR) of >90 mil/minute.1.73m2 [ Time Frame: wk48 ]
  • Urinary protein:urinary creatinine ratio of <0.2 [ Time Frame: wk48 ]
  • Inactive urinary sediment [ Time Frame: wk48 ]
Complete list of historical versions of study NCT00556192 on ClinicalTrials.gov Archive Site
-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 ] [ Designated as safety issue: Yes ]
  • The estimated GFR,urinary protein values and urinary sediment. [ Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 ]
  • Changes in disease activity score(SLEDAI) [ Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 ]
  • Other clinical features [ Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 ]
  • Duration of B-cell depletion [ Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 ]
  • Immunological parameters [ Time Frame: baseline,wk0,wk4,wk8,wk12,wk24,wk36,wk48 ]
Not Provided
Not Provided
 
Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy on Systemic Lupus Erythematosus
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Systemic Lupus Erythematosus
Drug: rituximab
  1. 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.
  2. 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.
  3. 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 Name: Mabthera
  • Active Comparator: 1
    Rituximab
    Intervention: Drug: rituximab
  • Active Comparator: 2
    Rituximab + Cyclophosphamide
    Intervention: Drug: rituximab
  • Active Comparator: 3
    Cyclophosphamide
    Intervention: Drug: rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
China
 
NCT00556192
SLE-2005-006
No
Lai-Shan Tam, Chinese University of Hong Kong
Chinese University of Hong Kong
Not Provided
Principal Investigator: Edmund Kwok Ming LI, MD Chinese University of Hong Kong
Chinese University of Hong Kong
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP