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

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 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Can Targeted Elimination of B-cell Depletion Therapy and/or Combination Therapy Restore Peripheral B Cell Abnormalities in Systemic Lupus Erythematosus(SLE)?

Resource links provided by NLM:

MedlinePlus related topics: Lupus

Drug Information available for: Cyclophosphamide Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Rituximab

U.S. FDA Resources

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
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Rituximab	Drug: rituximab 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 Name: Mabthera
Active Comparator: 2 Rituximab + Cyclophosphamide	Drug: rituximab 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 Name: Mabthera
Active Comparator: 3 Cyclophosphamide	Drug: rituximab 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 Name: Mabthera

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

No publications provided

Responsible Party:	Lai-Shan Tam, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:	NCT00556192 History of Changes
Other Study ID Numbers:	SLE-2005-006
Study First Received:	November 8, 2007
Last Updated:	February 10, 2012
Health Authority:	Hong Kong: Department of Health

Keywords provided by Chinese University of Hong Kong:

SLE
Rituximab
Methylprednisolone
Cyclophosphamide

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Rituximab
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on May 23, 2013