Study of Therapeutic Monitoring of Mycophenolate Mofetil (MMF/CellCept) After Kidney Transplantation

An Open-Label, Prospective, Randomized, Controlled, Multi-Center Study Assessing Fixed Dose Versus Concentration Controlled Cellcept® Regimens for Patients Following a Single Organ Renal Transplantation in Combination With Full Dose and Reduced Dose Calcineurin Inhibitors

This three-arm study will evaluate the efficacy and safety of various dosing regimens of MMF combined with various dosing regimens of calcineurin inhibitor (CNI), either cyclosporine or tacrolimus, in participants who have undergone kidney transplantation. Participants will be randomized to one of three dosing regimens to receive concentration-controlled MMF with reduced CNI, concentration-controlled MMF with standard CNI, or fixed-dose MMF with standard CNI. Participants will be followed for 20-24 months after randomization.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Mycophenolate mofetil; Drug: Cyclosporine; Drug: Tacrolimus

• Study Type: Interventional
• Enrollment (Actual): 720
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Bakersfield, California, United States, 93309
    • Los Angeles, California, United States, 90048
    • Los Angeles, California, United States, 90057
    • San Francisco, California, United States, 94143-0116
  • Colorado
    • Denver, Colorado, United States, 80262
  • Florida
    • Gainesville, Florida, United States, 32610-0224
    • Jacksonville, Florida, United States, 32216
    • Miami, Florida, United States, 33101
    • Orlando, Florida, United States, 32804
    • Tampa, Florida, United States, 33606
  • Georgia
    • Augusta, Georgia, United States, 30912
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5124
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
    • Shreveport, Louisiana, United States, 71130
  • Maryland
    • Baltimore, Maryland, United States, 21287-8611
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02111
    • Burlington, Massachusetts, United States, 01805
    • Springfield, Massachusetts, United States, 01107
    • Worcester, Massachusetts, United States, 01655
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0362
    • Detroit, Michigan, United States, 48202-2689
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
    • Livingston, New Jersey, United States, 07039
  • New York
    • Bronx, New York, United States, 10467
    • Buffalo, New York, United States, 14203
    • Hawthorne, New York, United States, 10532
    • New York, New York, United States, 10032
    • New York, New York, United States, 10021
    • New York, New York, United States, 10029
    • Rochester, New York, United States, 14642-8410
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
    • Winston-salem, North Carolina, United States, 27157
  • North Dakota
    • Fargo, North Dakota, United States, 58122
  • Ohio
    • Cleveland, Ohio, United States, 44106
  • Oregon
    • Portland, Oregon, United States, 97210
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19140
    • Philadelphia, Pennsylvania, United States, 19102-1192
    • Pittsburgh, Pennsylvania, United States, 15212
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
  • Texas
    • Dallas, Texas, United States, 75246
    • San Antonio, Texas, United States, 78284
  • Utah
    • Salt Lake City, Utah, United States, 84132
  • Vermont
    • Burlington, Vermont, United States, 05401
  • Virginia
    • Falls Church, Virginia, United States, 22042-3300
    • Norfolk, Virginia, United States, 23502
  • Washington
    • Seattle, Washington, United States, 98104
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females 13-75 years of age
• Single organ recipient (kidney only) from living (related or unrelated) or cadaveric heart-beating donors
• Receiving first or second kidney transplant

Exclusion Criteria:

• Immunosuppressive therapy (except for 48 hours prior to transplantation and corticosteroid treatment) within previous 28 days for a first transplant and 3 months for a second transplant
• History of malignancy in last 5 years (except successfully treated localized non-melanoma skin cancer)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Monitored MMF + Reduced CNI; Group A will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or intravenous (IV) form. The initial dose will be at least 1 gram twice a day (BID) in adults and 600 milligrams per meter-squared (mg/m^2) in pediatrics. Subsequent doses will be adjusted to maintain blood mycophenolic acid (MPA) levels greater than or equal to (≥) 1.3 micrograms per milliliter (μg/mL) with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain reduced blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 nanograms per milliliter (ng/mL); Days 30-90, 125-165 ng/mL; Days 90 through end of study, 95-145 ng/mL. Tacrolimus target concentrations areas follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL; Days 90 through end of study, 3-5 ng/mL.	Drug: Mycophenolate mofetil; Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m^2 in pediatrics. In Groups A and B, subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. In Group C, subsequent doses are not to be adjusted, except in the case of unacceptable toxicity.; Other Names: CellCept; Drug: Cyclosporine; Cyclosporine will be given as 100-mg soft gelatin capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 125-165 ng/mL (reduced) or 250-270 ng/mL (full); Days 90 through end of study, 95-145 ng/mL (reduced) or 190-220 ng/mL (full).; Other Names: Neoral; Drug: Tacrolimus; Tacrolimus will be given as 1-mg and 5-mg capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL (reduced), 8-10 ng/mL (full); Days 90 through end of study, 3-5 ng/mL (reduced), 6-8 ng/mL (full).; Other Names: Prograf
Experimental: Group B: Monitored MMF + Full CNI; Group B will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m^2 in pediatrics. Subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.	Drug: Mycophenolate mofetil; Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m^2 in pediatrics. In Groups A and B, subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. In Group C, subsequent doses are not to be adjusted, except in the case of unacceptable toxicity.; Other Names: CellCept; Drug: Cyclosporine; Cyclosporine will be given as 100-mg soft gelatin capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 125-165 ng/mL (reduced) or 250-270 ng/mL (full); Days 90 through end of study, 95-145 ng/mL (reduced) or 190-220 ng/mL (full).; Other Names: Neoral; Drug: Tacrolimus; Tacrolimus will be given as 1-mg and 5-mg capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL (reduced), 8-10 ng/mL (full); Days 90 through end of study, 3-5 ng/mL (reduced), 6-8 ng/mL (full).; Other Names: Prograf
Experimental: Group C: Fixed MMF + Full CNI; Group C will receive fixed-dose MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The dose will be at least 1 gram BID in adults and 600 mg/m^2 in pediatrics. Subsequent doses are not to be adjusted, except in the case of unacceptable toxicity. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.	Drug: Mycophenolate mofetil; Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m^2 in pediatrics. In Groups A and B, subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. In Group C, subsequent doses are not to be adjusted, except in the case of unacceptable toxicity.; Other Names: CellCept; Drug: Cyclosporine; Cyclosporine will be given as 100-mg soft gelatin capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 125-165 ng/mL (reduced) or 250-270 ng/mL (full); Days 90 through end of study, 95-145 ng/mL (reduced) or 190-220 ng/mL (full).; Other Names: Neoral; Drug: Tacrolimus; Tacrolimus will be given as 1-mg and 5-mg capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL (reduced), 8-10 ng/mL (full); Days 90 through end of study, 3-5 ng/mL (reduced), 6-8 ng/mL (full).; Other Names: Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Treatment Failure During 12 Months Post-Transplantation	Month 12
Percent Change from Baseline in Calculated Glomerular Filtration Rate (GFR) at 12 Months Post-Transplantation	Baseline to Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation	Months 6, 20-24
Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR)	Months 6, 12, 20-24
Percentage of Participants by Number of BPAR Episodes	Months 6, 12, 20-24
Percentage of Participants Treated for Acute Rejection (AR)	Months 6, 12, 20-24
Percentage of Participants Who Experienced Graft Loss	Months 6, 12, 20-24
Percentage of Participants Who Died	Months 6, 12, 20-24
Percentage of Participants Who Discontinued Treatment with MMF	Months 6, 12, 20-24
Time to First BPAR Episode	Months 6, 12, 20-24
Time to Treatment Failure	Months 6, 12, 20-24
Percent Change from Baseline in Calculated GFR at 3, 6, and 20-24 Months Post-Transplantation	Baseline to Months 3, 6, 20-24

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: July 12, 2004
• First Submitted That Met QC Criteria: July 13, 2004
• First Posted (Estimate): July 14, 2004

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: ML17225