MEmbranous Nephropathy Trial Of Rituximab - Full Text View

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:

Drug Information available for: Cyclosporine Rituximab

U.S. FDA Resources

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 > 30% 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 30% of baseline values the drug will also be discontinued. If there has been a >30% 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 225 ng/ml. A persistent and otherwise unexplained increase in serum creatinine > 30% would prompt a new target (CsA = 100-150 ng/ml;) and if with dose reduction the creatinine does not return to baseline levels within 3 weeks, then a second target of (CsA = 50-100 ng/ml) 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

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 > 30% 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 30% of baseline values the drug will also be discontinued. If there has been a >30% 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 225 ng/ml. A persistent and otherwise unexplained increase in serum creatinine > 30% would prompt a new target (CsA = 100-150 ng/ml;) and if with dose reduction the creatinine does not return to baseline levels within 3 weeks, then a second target of (CsA = 50-100 ng/ml) 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

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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 RTX. Patients who previously responded to CSA/CNI after 3 months or relapsed off RTX after 6 months are eligible.

Contacts and Locations

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

Contacts

Contact: Fernando C Fervenza, M.D., Ph.D.	507-266-7083	fervenza.fernando@mayo.edu
Contact: Lori A Riess	507-266-1047	riess.lori@mayo.edu

Locations

United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35294
Contact: Dana Rizk, MD 205-934-9509 drizk@uab.edu
Contact: Teresa Chacana 205-934-7649 tchacana@uab.edu
Principal Investigator: Dana Rizk, MD
United States, California
Stanford University	Recruiting
San Francisco, California, United States, 94304
Contact: Richard Lafayette, MD 650-736-1822 czar@stanford.edu
Contact: Kshama Mehta 650-736-1822 krmehta@stanford.edu
Principal Investigator: Richard Lafayette, MD
Sub-Investigator: Neiha Arora, MD
Sub-Investigator: Preeti Nargund, MD
United States, Florida
Mayo Clinic Jacksonville	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Nabeel Aslam, MD 904-953-7259 aslam.nabeel@mayo.edu
Contact: Johnathan J. Wright, MHSc, CCRP 904-953-7521 wright.johnathan@mayo.edu
Principal Investigator: Nabeel Aslam, MD
United States, Illinois
John H. Stroger, Jr. Hospital of Cook County	Recruiting
Chicago, Illinois, United States, 60612
Contact: Amit Joshi, MD 312-864-4609 ajoshi@cookcountyhhs.org
Contact: Kalyani Perumal, MD 312-864-4620 kperumal@cookcountyhhs.org
Principal Investigator: Amit Joshi, MD
Sub-Investigator: Kalyani Perumal, MD
United States, Kansas
University of Kansas Medical Center	Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ellen McCarthy, MD 913-588-7609 emccarthy@kumc.edu
Contact: Beth Courtney 913-588-7691 bcourtney@kumc.edu
Principal Investigator: Ellen McCarthy, MD
Sub-Investigator: Sri Yarlagadda, MD
United States, Michigan
University of Michigan	Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Patrick Gipson, MD 734-615-5757 pgipson@med.umich.edu
Contact: Courtney Harkness 734-232-4851 harkneco@med.umich.edu
Principal Investigator: Patrick Gipson, MD
Sub-Investigator: Matthias Kretzler, MD
Sub-Investigator: Brett Plattner, MD
Sub-Investigator: Debbie Gipson, MD
United States, Minnesota
Mayo Clinic Rochester	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lori A Riess 507-266-1047 riess.lori@mayo.edu
Contact: Shirley A Jennison 507-255-0231 jennison.shirley@mayo.edu
Sub-Investigator: John J. Dillon, M.D., PhD
Sub-Investigator: Stephen B. Erickson, M.D., Ph.D
Sub-Investigator: Eddie L. Greene, M.D., Ph.D
Sub-Investigator: LaTonya J. Hickson, M.D., Ph.D
Sub-Investigator: Marie C. Hogan, M.D., Ph.D
Sub-Investigator: Nelson Leung, M.D., Ph.D
United States, New York
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Jai Radhakrishnan, MD 212-305-5020 jr55@columbia.edu
Contact: Irma Orbe 212-305-5038 io67@columbia.edu
Principal Investigator: Jai Radhakrishnan, MBBS, MD, MSc
Sub-Investigator: Andrew Bomback, MD
Sub-Investigator: Pietro Canetta, MD
Sub-Investigator: Jonathan Hogan, MD
United States, Ohio
MetroHealth System (Case Western Reserve University	Recruiting
Cleveland, Ohio, United States, 44109
Contact: John Sedor, MD 216-778-4993 john.sedor@case.edu
Contact: Cindy Newman 216-778-3237 cnewman@metrohealth.org
Principal Investigator: John Sedor, MD
Sub-Investigator: John O'Toole, MD
United States, Wisconsin
Medical College of Wisconsin, Froedtert Hospital	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Samuel Blumenthal, MD 414-384-2000 ssblumen@mcw.edu
Contact: Charlotte Klis 414-805-9075 cklis@mcw.edu
Principal Investigator: Samuel Blumenthal, MD
Sub-Investigator: Hariprasad Trivedi, MD
Canada, British Columbia
St. Paul's Hospital, Providence Health Care	Recruiting
Vancouver, British Columbia, Canada, V6Z1Y6
Contact: Adeera Levin, MD 604-682-2344 Alevin@providencehealth.bc.ca
Contact: Katy Vela 604-806-9460 Kvela@providencehealth.bc.ca
Principal Investigator: Adeera Levin, MD
Sub-Investigator: Sean Barbour, MD
Canada, Ontario
Toronto General Hospital	Recruiting
Toronto, Ontario, Canada, M5G2C4
Contact: Daniel Cattran, MD 416-340-4187 daniel.cattran@uhn.ca
Contact: Paul Ling 416-340-3514 pling@uhnresearch.ca
Principal Investigator: Daniel Cattran, MD, FRCPC
Sub-Investigator: Michelle Hladunewich, MD
Sub-Investigator: Heather Reich, MD

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:	April 15, 2013
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 June 17, 2013

MEmbranous Nephropathy Trial Of Rituximab (MENTOR)