MEmbranous Nephropathy Trial Of Rituximab (MENTOR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Fernando Fervenza, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01180036
First received: August 10, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The primary outcome of this study is to determine whether or not the B cell targeting with Rituximab is more effective than Cyclosporine in inducing long term remission of proteinuria.


Condition Intervention Phase
Idiopathic Membranous Nephropathy
Drug: Rituximab
Drug: Cyclosporine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: "A Randomized Controlled Trial of Rituximab Versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (IMN)"

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Remission status [ Time Frame: 24 months after randomization ] [ Designated as safety issue: Yes ]
    Complete remission or partial remission at 24 months after randomization will be the primary endpoint.


Secondary Outcome Measures:
  • Remission Status [ Time Frame: 6-24 months after randomization ] [ Designated as safety issue: Yes ]
    Relapse state at month 24 after randomization (Urine Protein) (UP) >3.5 after earlier CR or PR; CR(Complete Remission) or PR (Partial Remission), and CR alone at 6, 12, 18, and 24 after randomization; Time to CR or PR; Anti-PLA2R levels; Quality of life as measured by modified KDQOL; Adverse events; ESRD


Estimated Enrollment: 126
Study Start Date: November 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rituximab 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 CD19+ B cell count.
Drug: Rituximab
1000 mg, I.V. on Days 1 and 15 and will be retreated at month 6 independent of CD19+ B cell count
Other Name: Rituxan, MabThera
Active Comparator: Cyclosporine Treatment Arm
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.
Drug: Cyclosporine
Patients randomized to the Cyclosporine arm will be started at a dose of (CsA = 3.5 mg/kg/day p.o. divided into 2 doses for 12 months). Target trough CsA blood levels, as determined in whole blood by HPLC, are 125 to 175 ng/ml. A persistent and otherwise unexplained increase in serum creatinine >30% would prompt an approximate 25% dose reduction of CSA, aiming for a corresponding 25% reduction in CSA trough level. If with this dose reduction the creatinine does not return to within 30% of baseline levels within 3 weeks, then a second dose reduction of approximately 25% with similar reduction in CSA trough level will be used. If the creatinine does not fall to baseline values with this second dose reduction, the drug will be discontinued. At the end of 12 months, Cyclosporine will be tapered by 1/3 of the maintenance dose monthly and hence discontinued after 3 months.
Other Name: Sandimmune

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • ACEi and/or ARB, for >3 months prior to randomization and adequate blood pressure (target BP <130/80 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 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 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, 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/CNI, RTX or alkylating agents with either a CR or PR but relapsed off CSA/CNI after 3 months or relapsed off RTX or alkylating agent after 6 months are eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01180036

Contacts
Contact: Fernando C. Fervenza, MD, PhD 507-266-1045 fervenza.fernando@mayo.edu
Contact: Lori A. Riess 507-266-1047 riess.lori@mayo.edu

  Show 21 Study Locations
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Fernando C. Fervenza, M.D., Ph.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Fernando Fervenza, M.D., Ph.D, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01180036     History of Changes
Other Study ID Numbers: 10-003372
Study First Received: August 10, 2010
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Membranous Nephropathy

Additional relevant MeSH terms:
Glomerulonephritis, Membranous
Kidney Diseases
Glomerulonephritis
Nephritis
Urologic Diseases
Autoimmune Diseases
Immune System Diseases
Cyclosporins
Cyclosporine
Rituximab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 23, 2014