Clinical trial NCT01230502: Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation
Official title: Donor Specific Regulation (DSR) Guided Tacrolimus Withdrawal to Myfortic Monotherapy in Liver Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Liver Transplant
Keywords: immunosuppression
anti-rejection
immune tolerance
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2010-10-29
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine whether long-term maintenance therapy with a single drug (Myfortic) applied using advanced immunologic monitoring tools in selected patients can lead to superior native kidney function at 2 years without resulting in increased acute rejection episodes or deterioration of liver allograft function.

Detailed description: The hypothesis to be tested is that donor-microchimerism in specific cell populations promotes the development of donor-specific regulation which in turn allows for long-term maintenance therapy with a single drug (Myfortic) in selected patients leading to superior long-term outcomes. Subjects will be enrolled post-transplantation and will be liver transplant recipients who meet the eligibility and exclusion criteria. We will use post-transplant monitoring for donor-specific immunologic regulation (DSR+/ DSA negative) to direct the withdrawal of patients to Myfortic monotherapy. Donor microchimerism, DSR, DSA development will be performed on samples obtained every six months from patients on study. The ultimate objective of the study is to use immunologic monitoring to develop a rational approach to achieving individualized immunosuppression for liver transplant patients.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects, ages 18 years and older who have received a primary liver transplant from a deceased donor for end stage liver disease \*(ESLD).
* Women of child-bearing potential must have a negative serum pregnancy test at the time of screening and agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of study treatment.

Exclusion Criteria:

* Recipients of multi-organ transplants.
* Recipients with positive crossmatch with their donor (current or previously).
* Subjects with a screening white blood cell count ≤ 2,000 mm3 or absolute neutrophil count (ANC) ≤ 1000, platelet count ≤ 100,000 mm3.
* Recipients with a hematocrit \< 32.
* History of malignancy within 5 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
* Subjects who are positive for hepatitis C, hepatitis B surface antigen, or HIV.
* Subjects with previous intolerance to full dose MPA agent.
* Subjects with a history of acute rejection within 6 months prior to study enrollment.
* Subjects who have had chronic ductopenic rejection.
* Subjects who had rejection in the first-year post-transplant and are less than 3 years post-transplant.
* Subjects who had rejection requiring treatment with thymoglobulin or Orthoclone-OKT3 (OKT3) at anytime post-transplant.
* Original cause of ESLD related to autoimmune diseases such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
* Subjects who have received an investigational drug within 4 weeks of study entry.
* Subjects with a history of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.
* Female subjects who are pregnant or nursing or females who are unwilling to use contraception during the study.
* Subjects who are currently receiving any therapy for immunosuppression other than a MPA agent and tacrolimus.
* Subjects with a history of hepatocellular carcinoma (T2 \>).
* Subjects with severe coexisting disease or presenting with any unstable medical condition which could affect study objectives.
* Subjects who have a known hypersensitivity to tacrolimus or mycophenolate

Primary outcomes:
measure: Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
timeFrame: 6 months post enrollment/randomization
measure: Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
timeFrame: 12 months post enrollment/randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin- Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Will Burlingham, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Anthony D'Alessandro, MD
role: PRINCIPAL_INVESTIGATOR
References: