MEmbranous Nephropathy Trial Of Rituximab (MENTOR)
Idiopathic Membranous Nephropathy
About this trial
This is an interventional treatment trial for Idiopathic Membranous Nephropathy focused on measuring Membranous Nephropathy
Eligibility Criteria
Inclusion Criteria
- Idiopathic MN with diagnostic biopsy
- Female, must be post-menopausal, surgically sterile or practicing a medically approved method of contraception(no birth-control pill)
- Must be off prednisone or mycophenolate mofetil for >1 month and alkylating agents for >6 months.
- angiotensin-converting-enzyme inhibitor (ACEi) and/or Angiotensin II receptor blockers (ARB), for >3 months prior to randomization and adequate blood pressure (target BP <130/80 millimeter of mercury (mmHg) in >75% of the readings, but subjects with BP <140/80 mmHg in >75% of the readings will be eligible). Patients with documented evidence of >3 months treatment with maximal angiotensin II blockade, on an 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA) reductase inhibitor, and BP control (BP <140/80 mmHg in >75% of the readings) who remain with proteinuria >5g/24h may enter and be randomized to RTX/CSA without the need of the run-in/conservative phase of the study.
- Proteinuria >5g/24h on two 24-hour urine collection collected within 14 days of each other
- Estimated glomerular filtration rate (GFR) ≥40 ml/min/1.73m2 while taking ACEi/ARB therapy OR quantified endogenous creatinine clearance >40 ml/min/1.73m2 based on a 24-hour urine collection.
Exclusion Criteria
- Presence of active infection or a secondary cause of MN (e.g. hepatitis B, systemic lupus erythematosus (SLE), medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred <2 years prior to enrollment into the study.
- Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment.
- Pregnancy or breast feeding for safety reasons
- History of resistance to CSA (or other calcineurin inhibitors, e.g. tacrolimus), RTX or alkylating agents (e.g. Cytoxan). Patients who previously responded to CSA/Calcineurin Inhibitor (CNI), RTX or alkylating agents with either a complete remission (CR) or partial remission (PR) but relapsed off CSA/CNI after 3 months or relapsed off RTX or alkylating agent after 6 months are eligible.
Sites / Locations
- University of Alabama at Birmingham
- Mayo Clinic Scottsdale
- University of Arizona, Tucson
- Stanford University
- Mayo Clinic Jacksonville
- University of Miami Hospital and Clinics
- University of Kansas Medical Center
- University of Michigan
- Mayo Clinic Rochester
- University of Mississippi Medical Center
- Washington University School of Medicine
- New York University
- Columbia University Medical Center
- MetroHealth System (Case Western Reserve University)
- Cleveland Clinic
- Ohio State University
- University of Washington Medical Center
- Medical College of Wisconsin, Froedtert Hospital
- St. Paul's Hospital, Providence Health Care
- Toronto General Hospital
- Centre hospitalier universitaire de Quebec - Hotel-Dieu de Quebec
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Rituximab Treatment Arm
Cyclosporine Treatment Arm
Patients randomized to the RTX arm will receive 1000 mg IV on Days 1 and 15. Patients who achieve complete remission at 6 months will not be retreated. A second course of RTX 1000 mg IV will be administered at study month 6 for individuals who have not achieved a complete remission, but have achieved a minimum of >25% reduction in Time 0 proteinuria. Dosing at study month 6 will be independent of cluster of differentiation (CD) 19+ B cell count.
Patients randomized to the Cyclosporine arm will be started at a dose of CsA = 3.5 mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Target trough CsA blood levels are 125 to 175 ng/ml. Patients will have their doses adjusted according to their blood levels of CSA as monitored every 2 weeks until the target trough level is reached. If a complete remission is achieved by 6 months, CSA will be tapered and discontinued over a three-month period. If after 6 months there has not been a reduction in proteinuria of at least 25% of baseline values, the drug will also be discontinued. If there has been a >25% reduction in baseline proteinuria (but not complete remission) the CSA will be continued for an additional 6 months.