Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00441220




Registration number
NCT00441220
Ethics application status
Date submitted
27/02/2007
Date registered
28/02/2007
Date last updated
5/03/2009

Titles & IDs
Public title
Cyclophosphamide in Lupus Nephritis
Scientific title
Failure of Cyclophosphamide Therapy in Lupus Nephritis Patients: the Role of Bioactivation Phenotype and Genotype
Secondary ID [1] 0 0
ADHB3557
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
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.
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
- 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:

1. histological evidence from renal biopsy;

2. persistent proteinuria of >0.5 g/day or proteinuria >3+ on dipstick; or

3. 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Those who do not meet inclusion criteria

- Those patients in the retrospective study who have died

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2010
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
North Island
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland
Country [3] 0 0
New Zealand
State/province [3] 0 0
Manakau City

Funding & Sponsors
Primary sponsor type
Other
Name
University of Auckland, New Zealand
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Auckland District Health Board
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Counties Manukau Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Auckland Medical Research Foundation
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Arthritis New Zealand
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT00441220
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nuala Helsby, PhD
Address 0 0
Senior Lecturer in Molecular Medicine and Pathology, University of Auckland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Peter Gow, MBChB
Address 0 0
Country 0 0
Phone 0 0
09 2760000
Fax 0 0
Email 0 0
PGow@middlemore.co.nz
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00441220