A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00545402
First received: October 16, 2007
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

This 2 arm study will compare the efficacy and safety of two CellCept-containing treatment regimens in de novo liver transplant patients. Patients will be randomized into one of two groups, to receive either CellCept (at a starting dose of 3g/day po, adjusted according to exposure) standard dose tacrolimus and corticosteroids (10-15 mg/kg i.v. on day 0), or fixed dose CellCept 2g/day po, standard dose tacrolimus and corticosteroids (10-15mg/kg i.v. on day 0, then reducing from 20mg to 5mg over 6 months, and discontinuing after 6 months). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Liver Transplantation
Drug: Mycophenolate mofetil, adjusted dose
Drug: Tacrolimus
Drug: Corticosteroids, IV
Drug: Mycophenolate mofetil, Standard dose
Drug: Corticosteroids, PO
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Study Comparing the Effect of CellCept With Therapeutic Drug Monitoring, Tacrolimus and a Corticosteroid-sparing Regimen Versus Fixed Dose CellCept, Tacrolimus and Corticosteroids Maintained up to 6 Months, on Acute Rejection and Safety in Liver Transplant Patients.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment ] [ Designated as safety issue: No ]
    Banff criteria required at least 2 of the 3 following features for a histopathological diagnosis of acute rejection: portal inflammation, bile duct inflammation, and venous endothelial inflammation. Each item was graded from 0 to 3 where 0 equals (=) mild, 2 = moderate, and 3 = severe. The sum of the 3 individual scores, from 0 to 9, corresponded to the Rejection Activity Index (RAI). If RAI = 0, 1, or 2, there was no evidence of rejection. If RAI = 3, there was borderline acute rejection. If RAI = 4 or 5, there was mild acute rejection. If RAI = 6 or 7, there was moderate acute rejection. If RAI = 8 or 9, there was severe acute rejection.


Secondary Outcome Measures:
  • Percentage of Participants With Graft Loss [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment. ] [ Designated as safety issue: No ]
    Graft survival was defined as the time between the randomization date and the graft loss date. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.

  • Graft Survival [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment. ] [ Designated as safety issue: No ]
    The median time, in months, between randomization and graft loss event. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.

  • Overall Survival (OS) at Month 12 - Percentage of Participants With an Event [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    OS was defined as the time between the date of randomization and death up to Month 12. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.

  • Overall Survival at Month 12 [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The median time, in months, between randomization and OS event. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.

  • Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review [ Time Frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant.


Enrollment: 180
Study Start Date: November 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MMF, Adjusted Dose; Tacrolimus; Corticosteroids
Participants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0.
Drug: Mycophenolate mofetil, adjusted dose
3 g/d PO BID during meals from Day 0 to Day 4, followed by dose adjustment based on AUC using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12.
Other Name: CellCept
Drug: Tacrolimus
Target trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12
Drug: Corticosteroids, IV
10-15 mg/kg IV pre-operation on Day 0
Other Name: Solu-Medrol
Active Comparator: MMF, Standard Dose; Tacrolimus; Corticosteroids
Participants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.
Drug: Tacrolimus
Target trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12
Drug: Corticosteroids, IV
10-15 mg/kg IV pre-operation on Day 0
Other Name: Solu-Medrol
Drug: Mycophenolate mofetil, Standard dose
2 g/d PO BID during meals from Day 0 to Month 12
Other Name: CellCept
Drug: Corticosteroids, PO
20 mg/d QDS from Day 0 through Month 1; 15 mg/day, TID from the end of Month 1 through Month 2; 10 mg/d BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.
Other Name: Cortancyl

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • recipient of a first orthotopic liver transplant.

Exclusion Criteria:

  • history of organ transplants;
  • patient receiving a multi-organ transplant;
  • calculated creatinine clearance <=30mL/min before transplant;
  • leukocyte count < 2000/mm3 at randomization;
  • history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;
  • pregnant or breast-feeding females, or females of childbearing age not using effective contraception.
  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: NCT00545402

Locations
France
Besancon, France, 25030
Bordeaux, France, 33076
Caen, France, 14033
Clichy, France, 92118
Creteil, France, 94010
Grenoble, France, 38043
Lille, France, 59037
Lyon, France, 69317
Lyon cedex 3, France, 69437
Marseille, France, 13385
Montpellier, France, 34295
Nice, France, 06202
Paris, France, 75679
Rennes, France, 35033
Toulouse, France, 31059
Villejuif, France, 94804
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00545402     History of Changes
Other Study ID Numbers: ML21273
Study First Received: October 16, 2007
Results First Received: June 9, 2014
Last Updated: June 9, 2014
Health Authority: France:Agence francaise de securite sanitaire des produits de sante (AFSSAPS)

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014