Trial Search Results
Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
- Membranous nephropathy is associated with damage to the walls of the glomeruli, the small blood vessels in the kidneys that filter waste products from the blood. This damage causes leakage of blood proteins into the urine and is associated with low blood protein levels, high blood cholesterol values, and swelling of the legs. These problems can decrease or go away without treatment in about 25 percent of patients, but if they persist, some patients may experience impaired (or loss of) kidney function, blood vessel and heart disease, and a risk of forming blood clots in veins.
- Kidney biopsies that show that antibodies have been deposited along the glomeruli suggest that specialized cells of the immune system, called B and T cells, are causing damage to the kidneys through their increased activity. To suppress the action of B and T cells and to decrease the harmful deposits in the kidneys, drug treatments are required.
- Patients with membranous nephropathy are often treated with immunosuppressive drugs such as cyclosporine or cytoxan plus steroids that attempt to reduce or suppress the activity of the immune system, decrease antibody production, and reduce antibody deposits in the kidney. However, not everyone responds to these medications and the kidney disease can return in some patients when the drugs are stopped. Also, there are side effects associated with long term usage of these medications. Rituximab, a different immunosuppressant, has also been used for this purpose. Although cyclosporine and Rituximab have been used separately, they have not been tried in combination as a possible treatment for membranous nephropathy.
- To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy.
- Individuals 18 years of age and older who have been diagnosed with membranous nephropathy based on a kidney biopsy done within the preceding 24 months, and who have had excess levels of protein in the urine for at least 6 months based on urine and blood tests.
- Potential participants will be screened with an initial clinic evaluation and full medical history.
- Before the treatment, there will be a run-in period that will last up to 2 months. During this time, participants will be placed on a blood pressure lowering medication and will not take any other immunosuppressant medications.
- Participants will visit the NIH clinical center for a baseline evaluation, four intravenous infusions of rituximab, and also at 1- to 6-month intervals throughout the study.
- Active treatment period will involve a 6-month course of cyclosporine and a total of four doses of rituximab. Participants will take cyclosporine tablets twice daily, and have two infusions of rituximab given 2 weeks apart, After 6 months, the cyclosporine dose will slowly be decreased over several weeks and then completely discontinued. Participants will then receive another course (two doses 2 weeks apart) of rituximab, depending on results of blood work.
- Participants will have frequent blood and urine tests performed to monitor the results of treatment and reduce the chance of side effects.
Stanford is currently accepting patients for this trial.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Drug: Rituximab Infusion
- Drug: Oral Cyclosporine
- INCLUSION CRITERIA:
1. Ability and willingness to provide informed consent (adults greater than or equal
to 18 years).
2. Nephrotic range proteinuria that persists for at least 6 months greater than 3.5
grams /24 hours (based on 24 hour urine collection).
3. Nephrotic range proteinuria (>3.5 g/24 hours) that persists despite angiotensin
antagonist therapy (ACE inhibitor or ARB) for at least 2 months unless
4. Renal biopsy within the past 24 months must reveal typical changes of membranous
nephropathy by light and electron microscopy.
5. There is no evidence to suggest secondary forms of membranous nephropathy.
Diagnostic studies for the common causes of membranous nephropathy are listed
under Baseline evaluation. Additional studies will be obtained as indicated.
1. Age <18 years old
2. Estimated GFR<40 ml/min/1.73 m^2 (determined by the 4 variable version of the MDRD
Study prediction equation) while on ACEI/ARB therapy . Lab values from the preceding 2
months prior to enrollment will be used to assess eligibility.
3. Immunosuppressive medications or experimental medications of any type during the three
month period prior to initiating Rituximab and cyclosporine.
4. Prior exposure to cyclosporine or tacrolimus for more than 6 months and/or evidence of
intolerance or toxicity associated with cyclosporine treatment of any duration
including irreversible azotemia, liver dysfunction or hypertension.
5. Prior treatment with Rituximab.
6. Clinically significant medical conditions (i.e. severe heart failure NYHA class IV,
uncontrolled coronary artery disease/unstable angina), which in the opinion of the
investigator, could increase the subject s risk of participating in the study or could
confound the interpretation of the results of the study. Patients with a history of
arrhythmias will be evaluated by a cardiology consultant regarding recommendations as
Rituximab has been reported to exacerbate arrhythmias (in patients with rheumatoid
7. Active acute or chronic infection requiring antimicrobial therapy or serious viral
infection (HIV, hepatitis B or C, herpes simplex, varicella zoster virus, parvovirus).
8. Live viral vaccines within one month prior to Rituximab.
9. Pregnant women, nursing mothers or individuals (men or women) not practicing birth
The rationale is that the safety of Rituximab during pregnancy, lactation, and infancy
has not been determined. However, limited data indicate that rituximab is present in
human milk and the effect on the breastfed child and no data on the effect on milk
production. IgG molecules are known to cross the placenta and Rituximab has been
detected in the serum of infants exposed in utero. Limited data indicate that B cell
lymphocytopenia lasting less than six months can occur in infants exposed to Rituximab
in utero. Pregnancy is not recommended until at least one year after Rituximab
administration. Breastfeeding is not recommended during treatment with rituximab and
for 6 months after the last dose. In humans, cyclosporine crosses the placenta and
premature births and low birth weight are consistently observed. Cyclosporine enters
breast milk and may lead to immune suppression in the infant as well as the unknown
effects on growth or association with carcinogenesis.
10. Uncontrolled hypertension defined as BP >140/90 on >25% of measurements. Blood
pressures will be measured 3 times at each clinic visit after the patient has sat
quietly for at least 5 minutes.
11. Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal
cell carcinoma of the skin.
12. Clinical evidence of cirrhosis or chronic active liver disease sufficiently severe to
impair cyclosporine metabolism; this would include a prolonged prothrombin time.
Patients with abnormal liver function tests will be evaluated by the Hepatology
Consult Service to determine whether protocol participation is appropriate.
13. Cytopenia (neutrophils <1500/mm^3 and/or thrombocytopenia <75,000) and/or CD4 T cell
14. Diabetes mellitus.
Ages Eligible for Study
18 Years - 100 Years
Genders Eligible for Study