6804: Membranous Nephropathy Trial of Rituximab (MENTOR)
Status: Enrollment Completed
- Idiopathic Membranous Nephropathy
This is a study to look at whether the drug Rituximab is better than our current form of treatment, Cyclosporine, for treating individuals with membranous nephropathy. Membranous nephropathy is a type of kidney disease that affects the filters of the kidney and commonly leads to kidney failure. This study will compare whether the drug Rituximab, a drug that is given by intravenous infusion (directly into your vein) works as well as Cyclosporine (which is given as a pill) in terms of reducing protein loss in the urine and helping patients to enter remission (a period of time when the disease is not active). Protein loss in the urine occurs as a result of the damage caused by membranous nephropathy. Reducing protein loss has been shown to improve long-term survival of the kidney. It is believed that membranous nephropathy is caused by antibodies which are produced against the individual’s kidney (specifically the filter part), and lead to protein loss in the urine, kidney damage and as the kidneys are not able to filter waste products from the body, kidney failure. Both Rituximab and Cyclosporine suppress the body's immune system, which will prevent antibody formation, reduce the ongoing kidney damage and allow the kidneys to heal.
Participants in the two arms of the study will be compared at 24 months (12 months after stopping the medication). We will also assess which of the medications is safer, better tolerated and produces the most prolonged remission of the protein leak.
This will be a randomized clinical trial, meaning the decision about which drug individuals will receive (Cyclosporine or Rituximab) will be decided by a random method (like flipping a coin). Total study size will be 126 individuals from up to 25 participating institutions. Individual participants will be in the study for approximately 27 months, which will include up to 1 year on study medication and then 1 year of follow-up visits.
If you agree to be in the study, you will be asked to participate in the following:
Physical examination and blood work: You will have a physical examination and routine blood and urine tests to determine if you are eligible to take part in the study. If you have had any of the exams, tests or procedures involved in this study as part of your routine standard of care within 30 days of screening, you may not need to repeat them. It will be up to your study doctor to review and consider if the previous findings are appropriate to use.
Blood pressure and cholesterol medication check: Prior to treatment with the study drug, your study doctor will put you on non-immunosuppressive (will not affect your immune system) therapy (conservative therapy period) with an Angiotensin-converting enzyme (ACE) inhibitor and Angiotensin II receptor blocker (medication to control blood pressure) and a statin drug to control your cholesterol level. If your blood pressure control is not at target, you may receive additional medications.
Assignment to a treatment group: If at the end of this conservative therapy period you are still eligible to take part in this study, you will be randomly assigned to one of 2 groups:
- Rituximab group - 63 participants will receive two intravenous infusions (medication will be delivered directly into your vein) of Rituximab at Day 1 and 15 (series 1).Six-months after being assigned to your treatment group, you will have a 6-month post-randomization visit, in which your urine will be tested for protein (proteinuria). Participants who have been randomized to Rituximab but who do not have at least a 30% reduction in proteinuria will exit the study and not receive the second series of infusions that would take place at Day 181 and Day 195. Rituximab, the drug used in this study, is considered investigational, which means it has either not been approved by the Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug in this research study.
- Cyclosporine group - 63 participants will receive Cyclosporine, which will be taken as a pill by mouth twice daily. You will have a blood test every two weeks until levels of the drug are stable and at target. If after Six-months after being assigned to your treatment group, you will have a 6-month post-randomization visit, in which your urine will be tested for protein (proteinuria). Participants who do not have a reduction in proteinuria of at least 30% from their baseline values will exit the study. This drug, Cyclosporine, is considered investigational, which means it has either not been approved by the Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug in this research study.
For all participants
In addition to the above treatments, all participants will be asked to participate in the following tests or procedures:
- Confirmation of diagnosis - We will review your most recent kidney biopsy that you had as part of your standard of care to confirm the diagnosis.
- Baseline - You will have a physical exam, blood test, and random urine collection. You will also be asked to complete two 24-hour urine collections and fill out a Quality of Life Questionnaire which takes about 5 minutes to complete.
- Day 28: Blood test for Cyclosporine levels or B cell depletion by Rituximab.
- 3 month visit: You will have a physical exam, blood test and one 24-hour urine collection.
- 6 month visit: You will have a physical exam, blood test, and random urine collection You will also be asked to complete two 24-hour urine collections and fill out a Quality of Life Questionnaire.
- 9 month visit: You will have a physical exam, blood test and one 24-hour urine collection.
- 12 month visit: You will have a physical exam, blood test, and random urine collection. You will also be asked to complete two 24-hour urine collections and fill out a Quality of Life Questionnaire.
- 18 month visit: You will have a physical exam, blood draw and two 24 hour urine collections.
- 24 month visit: You will have a physical exam, blood test, and random urine collection. You will also be asked to complete two 24-hour urine collections and fill out a Quality of Life Questionnaire.
To be eligible to participate, you must:
- Have idiopathic membranous nephropathy that was diagnosed by renal (kidney) biopsy
- Be between 18 and 80 years
- Not be pregnant or able to become pregnant. (Female participants must be post-menopausal, surgically sterile or practicing a medically approved method of contraception (other than the birth-control pill))
- Be off prednisone or mycophenolate mofetil for more than 1 month and alkylating agents for more than 6 months
- Have well-controlled blood pressure. Treatment with an ACEi and/or ARB, for at least 3 months prior to randomization and adequate blood pressure control (target blood pressure is less than 130/80 mm Hg in more than 75% of the readings, but participants with blood pressure less than 140/80 mmHg in more than 75% of the readings will be considered eligible)
- Proteinuria more than 5g/24h while taking ACEi/ARB therapy
- Estimated GFR greater or equal to 40 ml/min/1.73m2 while taking ACEi/ARB therapy OR quantified endogenous creatinine clearance >40 ml/min based on a 24 hour urine collection as confirmed by lab tests.
You are not eligible to participate if you have:
- Have an active infection or a secondary cause of idiopathic membranous nephropathy (such as hepatitis B, lupus, medications, malignancies).
- Have Type 1 or 2 diabetes mellitus
- Are pregnant or breast feeding
- Have a history of resistance to cyclosporine or rituximab
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.
For general information about the study or for a complete list of participating institutions, please e-mail Karen Pope at the MENTOR Data Management and Coordination Center (firstname.lastname@example.org)
- New York
University of Alabama at Birmingham
Teresa Chacana, Research Coordinator
John H. Stroger, Jr. Hospital of Cook County
Ekpeno Nnah, Research Coordinator
Kansas University Medical Center
Beth Courtney, Research Coordinator
University of Michigan
Courtney Harkness, Research Coordinator
Columbia University Medical Center, New York
Irma Orbe, Research Coordinator
New York University, New York
Emily Tavarez, Research Coordinator
Sue Saunders, Research Coordinator
The MetroHealth System (Case Western University), Cleveland
Cindy Newman, Research Coordinator
Ohio State University, Columbus
Sarah Hasselbach, Research Coordinator
Medical College of Wisconsin, Froedtert Hospital
Charlotte Klis, Research Coordinator
St. Paul's Hospital, Providence Health Care, Vancouver
Katy Vela, Research Coordinator
University Health Network, Toronto General Hospital, Toronto
Contact: Paul Ling