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Can Targeted Elimination of B-Cell Depletion Therapy and/or Combination Therapy on Systemic Lupus Erythematosus
This study is ongoing, but not recruiting participants.
Sponsored by: Chinese University of Hong Kong
Information provided by: Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT00556192
  Purpose

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.


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: rituximab
Phase II

MedlinePlus related topics: Lupus
Drug Information available for: Cyclophosphamide Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate Rituximab Azathioprine Azathioprine sodium salt BaseLine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Can Targeted Elimination of B-Cell Depletion Therapy and/or Combination Therapy Restore Peripheral B Cell Abnormalities in Systemic Lupus Erythematosus(SLE)?

Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • -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 ]

Secondary Outcome Measures:
  • -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 ]

Estimated Enrollment: 20
Study Start Date: June 2006
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
Rituximab
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.
2: Active Comparator
Rituximab + Cyclophosphamide
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.
3: Active Comparator
Cyclophosphamide
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00556192

Locations
China
Department of Medicine and Therapeutics
Hong Kong, China
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Edmund Kwok Ming LI, MD Chinese University of Hong Kong
  More Information

Responsible Party: The Chinese University of Hong Kong ( Lai-Shan Tam )
Study ID Numbers: SLE-2005-006
Study First Received: November 8, 2007
Last Updated: May 7, 2008
ClinicalTrials.gov Identifier: NCT00556192  
Health Authority: Hong Kong: Department of Health

Keywords provided by Chinese University of Hong Kong:
SLE
Rituximab
Methylprednisolone
Cyclophosphamide

Study placed in the following topic categories:
Azathioprine
Autoimmune Diseases
Lupus Erythematosus, Systemic
Methylprednisolone
Rituximab
Prednisolone
Connective Tissue Diseases
Methylprednisolone acetate
Prednisolone acetate
Cyclophosphamide
Congenital Abnormalities
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Hormones
Glucocorticoids
Protective Agents
Neuroprotective Agents
Immunosuppressive Agents
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009