Cyclophosphamide in Lupus Nephritis
Failure of Cyclophosphamide Therapy in Lupus Nephritis Patients: the Role of Bioactivation Phenotype and Genotype
1 other identifier
observational
60
1 country
3
Brief Summary
Cyclophosphamide is widely used in the treatment of cancer and autoimmune diseases such as lupus nephritis. However, there is considerable variability in the response to cyclophosphamide treatment. Cyclophosphamide is a pro-drug that requires initial activation by CYP liver enzymes. Recent clinical studies have indicated a possible role of one CYP enzyme, CYP2C19 in this activation step. This enzyme has a genetic polymorphism (variants which lack functional activity) and people who have inherited these variants are poor metabolisers of certain drugs. The aim of this study is to determine whether response to therapy in a New Zealand population of lupus nephritis patients is determined by cyclophosphamide bioactivation (the metabolic phenotype) and CYP genotype. Currently there is no way of predicting a patient's response to cyclophosphamide. An understanding of the factors which contribute to the therapeutic failure in lupus nephritis is particularly important due to the high morbidity and mortality associated with this disease. There are other treatment options for lupus nephritis patients who fail to respond to cyclophosphamide. If successful, this study may help identify patients who are unlikely to respond to cyclophosphamide and thus should not be unnecessarily be exposed to the drug and may justify the use of newer, more costly immunosuppressive drugs such as mycophenolate mofetil and rituximab.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Oct 2006
Longer than P75 for all trials
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2006
CompletedFirst Submitted
Initial submission to the registry
February 27, 2007
CompletedFirst Posted
Study publicly available on registry
February 28, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2010
CompletedMarch 5, 2009
February 1, 2009
February 27, 2007
March 4, 2009
Conditions
Keywords
Study Arms (2)
A
Patients must have lupus nephritis and previously had therapy with intravenous cyclophosphamide.
B
Patients must have lupus nephritis and are currently receiving therapy with intravenous cyclophosphamide.
Eligibility Criteria
Patients with lupus nephritis who are receiving or have previously received intravenous cyclophosphamide.
You may qualify if:
- Patients with lupus nephritis requiring therapy with intravenous cyclophosphamide
- Lupus nephritis is defined according to American College of Rheumatology criteria as the presence of either:
- histological evidence from renal biopsy;
- persistent proteinuria of \>0.5 g/day or proteinuria \>3+ on dipstick; or
- cellular casts of any type. Patients will have had a renal biopsy performed to determine the histological class of lupus nephritis. Therapy with cyclophosphamide is typically used in patients with Class III, IV and severe Class V lupus nephritis.
- Patients ≥ 18 years of age
- Patients must be able to provide informed consent
You may not qualify if:
- Those patients in the retrospective study who have died
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Auckland, New Zealandlead
- Auckland District Health Boardcollaborator
- Counties Manukau Healthcollaborator
- Auckland Medical Research Foundationcollaborator
- Arthritis New Zealandcollaborator
Study Sites (3)
Auckland City Hospital
Auckland, North Island, New Zealand
University Of Auckland
Auckland, New Zealand
Middlemore Hospital
Manakau, Private Bag 93311, New Zealand
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nuala Helsby, PhD
Senior Lecturer in Molecular Medicine and Pathology, University of Auckland
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
February 27, 2007
First Posted
February 28, 2007
Study Start
October 1, 2006
Study Completion
October 1, 2010
Last Updated
March 5, 2009
Record last verified: 2009-02