Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation
Condition: Graft Rejection
Intervention: Alemtuzumab; Anti-Thymocyte Globulin
Intervention description: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.; 1.5 mg/kg per dose through a central line intraoperatively and on POD# 2 and 4, then continue on alternate days until a therapeutic tacrolimus(or cyclosporine) level is achieved, or until the SCr < 3-4 mg/dL.
Give first dose over 6 hours, subsequent doses over 4 hours.
Premedication to be given with the first 3 doses:
Tylenol 650mg PO/PR Benadryl 25-50mg PO/IV Daily scheduled corticosteroid dose or other corticosteroid as deemed appropriate.
Hold infusion if temperature > 100.5ºF; Adjust dose for low WBC or Plt count Peripheral Thymoglobulin administration: Prepare dose in 500cc NS; Add heparin 1,000 units and hydrocortisone 20mg to the bag; Infuse over a minimum of 6 hours
Intervention MeSH terms: Alemtuzumab; Antilymphocyte Serum
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 222.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Renal Transplantation; Pancreas Transplantation; Graft Rejection; Immunosuppression; Kidney failure, chronic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Summary:

      The purpose of this research study is to compare the effects of the two most commonly used
      anti-T cell induction agents(alemtuzumab and rabbit anti-thymocyte globulin) to prevent
      rejection in kidney and pancreas transplant patients. Alemtuzumab is Food and Drug
      Administration (FDA) approved for treating a certain type of cancer (leukemia), and
      Thymoglobulin® (rabbit anti-thymocyte globulin) is approved for anti-rejection treatment, but
      neither drug is FDA approved for administration at the time of transplantation to help
      prevent rejection. Even so, many transplant centers use these medications at the time of
      transplantation and believe that their use helps to decrease the risk of developing rejection
      following kidney and pancreas transplantation. Which drug might be better is not known.
      Subjects will receive either alemtuzumab (one administration) or rabbit anti-thymocyte (3 to
      7 doses) at and within the first week of transplantation. Subjects will be assigned to either
      the alemtuzumab or rabbit anti-thymocyte globulin groups by chance. The two groups will be
      compared to see if there are meaningful differences for survival, organ function, side
      effects, and quality of life. The follow-up care after transplant for subjects in the study
      is the same as that for patients who are not in the study, except that a quality of life
      questionnaire (estimated to take 10 minutes to complete) will be completed at the time of
      transplant and through year 2 during selected scheduled clinic visits. A retrospective chart
      review will occur at 3-5 years post-transplant to follow incidence of chronic rejection,
      patient and graft survival and graft function.
    

Eligibility criteria:

        Enrollment of kidney transplant patients has been completed. The protocol has been amended
        to enroll 50 additional subjects who will receive either a simultaneous pancreas and kidney
        transplant, pancreas after kidney transplant, or solitary pancreas transplant.

        Inclusion Criteria:

          -  Male or female patients who receive a simultaneous pancreas and kidney transplant,
             pancreas after kidney transplant, or solitary pancreas transplant

          -  Age 18 to 65

          -  Females of child bearing potential must have a negative pregnancy test at time of
             transplant

          -  Ability to give informed consent

        Exclusion Criteria:

          -  Inability to give informed consent

          -  ABO incompatibility

          -  T-cell or B-cell positive cross match

          -  Patients with a previous hypersensitivity to alemtuzumab, anti-thymocyte globulin, or
             any monoclonal or polyclonal antibody preparation

          -  Current active infection (currently receiving antibiotics, treatment for active
             infection within 1 week of transplant, or medical judgement)

          -  Hepatitis B surface antigen positive

          -  Human immunodeficiency virus positive

          -  Any malignancy within 2 years except for successfully treated basal or squamous cell
             carcinoma of skin

          -  Pregnancy

          -  Breast feeding women