This is a prospective multicenter, open-label, single-arm trial in which 211 recipients of liver allografts receive a uniform immunosuppressive induction and maintenance regimen. Participants with end-stage liver disease who meet the entry criteria are consented and enrolled. Participants receive antibody induction with Campath-1H and maintenance immunosuppression with tacrolimus. Tacrolimus monotherapy is maintained for at least 12 months. Assessments of immunological status including liver graft biopsies are performed. At 12 months, participants are assessed for immune reconstitution and for the ability to undergo tapering and subsequent withdrawal of immunosuppression. A decision about the appropriateness of withdrawal is made for each individual.

Study hypothesis: Liver transplant patients receiving a Campath 1H induction therapy and tacrolimus monotherapy as maintenance immunosuppression can undergo successful tapering and subsequent withdrawal of immunosuppression.

Condition	Treatment or Intervention	Phase
Liver Transplantation	Drug: Campath 1H  Drug: Tacrolimus (FK506, "Prograf")	Phase II

Further Study Details: 

Primary Outcomes: Proportion of participants who have graft loss or death within 1 year of transplantation
Expected Total Enrollment:  211

The study aims to address a primary endpoint of safety and efficacy. More importantly, the study will focus on correlations of clinical and mechanistic data to look for profiles that may relate to immune tolerance and whether a patient will reject. Patients will receive two infusions containing 30 mg of Campath-1H: one on the day of transplant right before receiving the new organ, and one on the fourth day after transplant. Starting 24 hours post-transplant, patients will begin receiving tacrolimus monotherapy. Prophylactic medications will be administered to deter opportunistic infections until immune reconstitution is satisfactory. For patients who develop a sensitivity to tacrolimus, cyclosporine can be substituted. For patients who qualify at least 1 year after transplant, they will be consented and begin a 12-month withdrawal of tacrolimus, followed by a two-year follow-up period with 6-month visits to gather immunological data and monthly visits to monitor liver function while off of immunosuppression. Patients who remain on tacrolimus and are not eligible for withdrawal will be followed for one year, completing two semi-annual visits to collect immunological and clinical data. A battery of immunological testing will be done at numerous core laboratories.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Necessity for liver transplant.
• A negative pregnancy test at study entry for females of child-bearing potential.
• For participants with reproductive potential, agreement to use approved methods of birth control for the duration of their participation.
• Ability to provide informed consent.
• Availability of donor spleen.

Exclusion Criteria

• Previous transplant
• multiorgan transplant or living donor transplant
• Donor liver from a donor positive for antibody against hepatitis B core antigen or hepatitis C.
• Donor liver from a non–heart-beating donor.
• Liver failure due to autoimmune disease, such as autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis.
• Hepatitis B or C infection
• Stage III or higher hepatocellular cancer based on pretransplant imaging
• History of malignancy except hepatocellular cancer, adequately treated in situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of skin.
• Active systemic infection at the time of transplantation.
• Clinically significant chronic renal disease, cardiovascular or cerebrovascular disease.
• HIV infection
• Any investigational drug received within 6 weeks of study entry.
• Hypersensitivity to Campath-1H or tacrolimus.

California
      University of California San Francisco, San Francisco,  California,  94143,  United States; Recruiting
Colorado
      University of Colorado, Denver,  Colorado,  80262,  United States; Not yet recruiting
Florida
      University of Miami School of Medicine, Miami,  Florida,  33101,  United States; Recruiting
Illinois
      University of Chicago, Chicago,  Illinois,  60637,  United States; Recruiting
Louisiana
      Ochsner Clinic, New Orleans,  Louisiana,  70121,  United States; Not yet recruiting
Michigan
      University of Michigan, Ann Arbor,  Michigan,  48109,  United States; Not yet recruiting
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States; Not yet recruiting
New York
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
Ohio
      Cleveland Clinic, Cleveland,  Ohio,  44195,  United States; Not yet recruiting
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States; Not yet recruiting
Tennessee
      University of Tennessee, Memphis,  Tennessee,  38163,  United States; Not yet recruiting
Texas
      Baylor University, Dallas,  Texas,  75246,  United States; Recruiting
Wisconsin
      University of Wisconsin, Madison,  Wisconsin,  53792,  United States; Recruiting
Canada, Alberta
      University of Alberta, Edmonton,  Alberta,  Canada; Not yet recruiting

Study chairs or principal investigators

J. Richard Thistlethwaite, MD,  Principal Investigator,  University of Chicago   

Study ID Numbers:  ITN024ST
Record last reviewed:  March 2005
Last Updated:  March 18, 2005
Record first received:  March 10, 2005
ClinicalTrials.gov Identifier:  NCT00105235
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08