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

Liver Transplantation Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545402
• Other study ID #: ML21273
• Status: Completed
• Phase: Phase 4
• First received: October 16, 2007
• Last updated: June 9, 2014
• Start date: November 2007
• Est. completion date: July 2011

Study information

• Verified date: June 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France:Agence francaise de securite sanitaire des produits de sante (AFSSAPS)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

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.
• 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
• Corticosteroids, IV
10-15 mg/kg IV pre-operation on Day 0
• Mycophenolate mofetil, Standard dose
2 g/d PO BID during meals from Day 0 to Month 12
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant	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.	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	No
Secondary	Percentage of Participants With Graft Loss	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.	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.	No
Secondary	Graft Survival	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.	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.	No
Secondary	Overall Survival (OS) at Month 12 - Percentage of Participants With an Event	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.	Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12	No
Secondary	Overall Survival at Month 12	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.	Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review	The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant.	Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12	No