A Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

Systemic Lupus Erythematosus Clinical Trial

— SLE  

Official title:

Prospective Study Based on Genetic Polymorphisms Related to Individual Variations of Side Effects of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689350
• Other study ID #: 2012ZX09506001-004
• Status: Completed
• Phase: N/A
• First received: September 17, 2012
• Last updated: August 27, 2014
• Start date: October 2012
• Est. completion date: March 2014

Study information

• Verified date: August 2014
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: National Natural Science Foundation
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Years to 60 Years

Eligibility

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.

1. Malar rash (rash on cheeks).

2. Discoid rash (red, scaly patches on skin that cause scarring).

3. Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart).

4. Oral ulcers (includes oral or nasopharyngeal ulcers).

5. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion.

6. Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups).

7. 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.

8. Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope.

9. Antinuclear antibody test positive.

10. 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).

11. 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;

1. HIV (-);

2. Signed the informed consent;

3. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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).

Locations

Country	Name	City	State
China	School of Pharmaceutical Sciences Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	First Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	one month	Yes
Secondary	Adverse Reaction ( Infection )	Flu-like symptoms, Upper respiratory tract infection,and the etc.	one month	Yes