Back to resultsA Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment (SLE)
Primary Purpose
Systemic Lupus Erythematosus
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Genotype Detection
Sponsored by
About this trial
This is an interventional supportive care trial for Systemic Lupus Erythematosus focused on measuring Cyclophosphamide, genotype-based therapy, prospective study
Eligibility Criteria
Inclusion Criteria:
The American College of Rheumatology established eleven criteria in 1982,which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials.
- Malar rash (rash on cheeks).
- Discoid rash (red, scaly patches on skin that cause scarring).
- Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart).
- Oral ulcers (includes oral or nasopharyngeal ulcers).
- Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion.
- Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups).
- Blood-hematologic disorder-hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/µl), lymphopenia (<1500/µl) or thrombocytopenia (<100000/µl) in the absence of offending drug. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.
- Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope.
- Antinuclear antibody test positive.
- Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons).
- Neurologic disorder: Seizures or psychosis. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. In the meantime, the case has one of the following conditions or more;
- HIV (-);
- Signed the informed consent;
- Taking contraceptive measures during treatment period.
Exclusion Criteria:
- Poor compliance;
- With lupus mental damage complication, occurrence of epilepsy or unable to express subjective symptoms during the observation period.
- Taking drugs that affect cytochrome P450 2B6, cytochrome P450 3A4 and cytochrome P450 2C19, except corticosteroids.
- Abnormal liver function.
Sites / Locations
- School of Pharmaceutical Sciences Sun Yat-sen University
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control Group
Experimental Group
Arm Description
The cases in control group received traditional therapy that the initial dose of cyclophosphamide (CPA) was 0.2-0.6g/week injection according to clinical experience.
Genetic: Genotype Detection To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM),with initial dose of CPA as 0.2g, 0.4g and 0.6g per week by injection, respectively.
Outcomes
Primary Outcome Measures
Adverse Reaction (Leucopenia)
The count of white cells < 4.0 × 10ˆ9/L in SLE patient who received CPA medication was considered as CPA-induced leucopenia.
Secondary Outcome Measures
Adverse Reaction ( Infection )
Flu-like symptoms, Upper respiratory tract infection，and the etc.
Full Information
NCT ID
NCT01689350
First Posted
September 17, 2012
Last Updated
August 27, 2014
Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University
1. Study Identification
Unique Protocol Identification Number
NCT01689350
Brief Title
A Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment
Acronym
SLE
Official Title
Prospective Study Based on Genetic Polymorphisms Related to Individual Variations of Side Effects of Cyclophosphamide in Systemic Lupus Erythematosus Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription.
Detailed Description
Cyclophosphamide (CPA) has been one of the most successful therapies for severe Systemic lupus erythematosus (SLE). However, cyclophosphamide can cause severe side effects, including bone marrow suppression, infection, gastrointestinal reaction, hemorrhagic cystitis, and the etc. Significant variation in efficacy and toxicity of CPA has been observed. Since the development of applicable therapeutic drug monitoring (TDM) of cyclophosphamide has been reported, it will help to improve the efficacy and reduce toxicities in SLE treatment. However, the TDM is a passive strategy which usually lags behind the appearance of toxicities. Therefore，it is especially crucial to give individuals genotype-based personal prescription of cyclophosphamide in order to gain the most effective therapies. Thus, the purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription, in order to verify the efficacy of the genotype-based personal prescription.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
Cyclophosphamide, genotype-based therapy, prospective study
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
The cases in control group received traditional therapy that the initial dose of cyclophosphamide (CPA) was 0.2-0.6g/week injection according to clinical experience.
Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
Genetic: Genotype Detection To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM),with initial dose of CPA as 0.2g, 0.4g and 0.6g per week by injection, respectively.
Intervention Type
Genetic
Intervention Name(s)
Genotype Detection
Intervention Description
To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM).
Primary Outcome Measure Information:
Title
Adverse Reaction (Leucopenia)
Description
The count of white cells < 4.0 × 10ˆ9/L in SLE patient who received CPA medication was considered as CPA-induced leucopenia.
Time Frame
one month
Secondary Outcome Measure Information:
Title
Adverse Reaction ( Infection )
Description
Flu-like symptoms, Upper respiratory tract infection，and the etc.
Time Frame
one month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
The American College of Rheumatology established eleven criteria in 1982,which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials.
Malar rash (rash on cheeks).
Discoid rash (red, scaly patches on skin that cause scarring).
Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart).
Oral ulcers (includes oral or nasopharyngeal ulcers).
Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion.
Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups).
Blood-hematologic disorder-hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/µl), lymphopenia (<1500/µl) or thrombocytopenia (<100000/µl) in the absence of offending drug. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.
Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope.
Antinuclear antibody test positive.
Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons).
Neurologic disorder: Seizures or psychosis. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. In the meantime, the case has one of the following conditions or more;
HIV (-);
Signed the informed consent;
Taking contraceptive measures during treatment period.
Exclusion Criteria:
Poor compliance;
With lupus mental damage complication, occurrence of epilepsy or unable to express subjective symptoms during the observation period.
Taking drugs that affect cytochrome P450 2B6, cytochrome P450 3A4 and cytochrome P450 2C19, except corticosteroids.
Abnormal liver function.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huang Min, PhD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Chair
Facility Information:
Facility Name
School of Pharmaceutical Sciences Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510006
Country
China
12. IPD Sharing Statement
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A Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment
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