RECRUITING

Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy

Conditions

Nephrotic Syndrome Proteinuria Autoimmune Disease Glomerular Disease Membranous Glomerulonephritis Kidney Disease Autoimmune Diseases Clinical Trial

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: * 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. Objectives: - To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy. Eligibility: - 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. Design: * 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.

Official Title

Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy

Quick Facts

Study Start:2010-12-22

Study Completion:2025-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT00977977

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Stated willingness to comply with all study procedures and availability for the duration of the study 2. Male or female, \>= 18 years of age 3. Nephrotic range proteinuria that persists for at least 6 months post diagnosis of membranous nephropathy greater than 3.5 grams /24 hours (based on 24-hour urine collection). 4. Nephrotic range proteinuria (\>3.5 g/24 hours) that persists despite angiotensin antagonist therapy (ACE inhibitor or ARB) for at least 2 months unless intolerant. 5. Renal biopsy within the past 24 months must reveal typical changes of membranous nephropathy by light and electron microscopy or a positive anti-PLA2R antibody test in the serum. There has been a change in the management strategies for MN such that a renal biopsy is not absolutely required for diagnosis if patient has positive circulating anti-PLA2R antibody. 6. Blood pressure \<=140/90 on \>75% of measurement while on anti-hypertensive treatment for at least 1-2 months. 7. There is no evidence to suggest secondary forms of membranous nephropathy. 8. Ability to take oral medication and be willing to adhere to the cyclosporine regimen 9. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for 12 months after the last Rituximab infusion. 10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. 11. Ability of subject to understand and the willingness to sign a written informed consent document.	1. Estimated GFR\<40 ml/min/1.73 m\^2 from the preceding 2 months prior to enrollment while on ACEI/ARB therapy. 2. Immunosuppressive medications or experimental medications of any type during the three-month period prior to initiating Rituximab and cyclosporine. 3. 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 4. Rituximab use within the previous 12 months. 5. 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. 6. Positive HIV serology 7. Positive HCV serology 8. Active acute or chronic infection requiring antimicrobial therapy or serious viral infection cytomegalovirus, herpes simplex, varicella zoster virus (chicken pox or shingles), Parvovirus B19 (can be based on previous medical records within the past 24-months) 9. Live viral vaccines within one month prior to Rituximab. 10. Pregnancy or lactation 11. Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell carcinoma of the skin. The rationale is that immunosuppression may accelerate cancer progression. 12. Clinical evidence of cirrhosis or chronic active liver disease sufficiently severe to impair cyclosporine metabolism; this would include a prolonged prothrombin time. 13. Cytopenia (neutrophils \<1500/mm\^3 and/or thrombocytopenia \<75,000) and/or CD4 T cell count \<200/mm\^3). The rationale is that Rituximab therapy may be followed by cytopenia with the granulocyte lineage being at greatest risk. Patients with low CD4 T cell counts are prone to infection which can be exacerbated by Rituximab. 14. Diabetes mellitus. The rationale is that diabetes may lead to worsening of proteinuria that would not respond to immunosuppression and would confound the results.

Inclusion Criteria

Exclusion Criteria

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Male or female, \>= 18 years of age
3. Nephrotic range proteinuria that persists for at least 6 months post diagnosis of membranous nephropathy greater than 3.5 grams /24 hours (based on 24-hour urine collection).
4. Nephrotic range proteinuria (\>3.5 g/24 hours) that persists despite angiotensin antagonist therapy (ACE inhibitor or ARB) for at least 2 months unless intolerant.
5. Renal biopsy within the past 24 months must reveal typical changes of membranous nephropathy by light and electron microscopy or a positive anti-PLA2R antibody test in the serum. There has been a change in the management strategies for MN such that a renal biopsy is not absolutely required for diagnosis if patient has positive circulating anti-PLA2R antibody.
6. Blood pressure \<=140/90 on \>75% of measurement while on anti-hypertensive treatment for at least 1-2 months.
7. There is no evidence to suggest secondary forms of membranous nephropathy.
8. Ability to take oral medication and be willing to adhere to the cyclosporine regimen
9. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for 12 months after the last Rituximab infusion.
10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
11. Ability of subject to understand and the willingness to sign a written informed consent document.

1. Estimated GFR\<40 ml/min/1.73 m\^2 from the preceding 2 months prior to enrollment while on ACEI/ARB therapy.
2. Immunosuppressive medications or experimental medications of any type during the three-month period prior to initiating Rituximab and cyclosporine.
3. 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
4. Rituximab use within the previous 12 months.
5. 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.
6. Positive HIV serology
7. Positive HCV serology
8. Active acute or chronic infection requiring antimicrobial therapy or serious viral infection cytomegalovirus, herpes simplex, varicella zoster virus (chicken pox or shingles), Parvovirus B19 (can be based on previous medical records within the past 24-months)
9. Live viral vaccines within one month prior to Rituximab.
10. Pregnancy or lactation
11. Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell carcinoma of the skin. The rationale is that immunosuppression may accelerate cancer progression.
12. Clinical evidence of cirrhosis or chronic active liver disease sufficiently severe to impair cyclosporine metabolism; this would include a prolonged prothrombin time.
13. Cytopenia (neutrophils \<1500/mm\^3 and/or thrombocytopenia \<75,000) and/or CD4 T cell count \<200/mm\^3). The rationale is that Rituximab therapy may be followed by cytopenia with the granulocyte lineage being at greatest risk. Patients with low CD4 T cell counts are prone to infection which can be exacerbated by Rituximab.
14. Diabetes mellitus. The rationale is that diabetes may lead to worsening of proteinuria that would not respond to immunosuppression and would confound the results.

Contacts and Locations

Study Contact

Meryl A Waldman, M.D.

CONTACT

(301) 451-6990

waldmanm@mail.nih.gov

Principal Investigator

Meryl A Waldman, M.D.

PRINCIPAL_INVESTIGATOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Locations (Sites)

National Naval Medical Center

Bethesda, Maryland, 20889

United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Meryl A Waldman, M.D., PRINCIPAL_INVESTIGATOR, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2010-12-22

Study Completion Date2025-01-31

Study Record Updates

Study Start Date2010-12-22

Study Completion Date2025-01-31

Terms related to this study

Keywords Provided by Researchers

Kidney Disease
Nephrotic Syndrome
Autoimmune Diseases
Clinical Trial
Proteinuria

Additional Relevant MeSH Terms

Nephrotic Syndrome
Proteinuria
Autoimmune Disease
Glomerular Disease
Membranous Glomerulonephritis