Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow With Kidney Transplantation Patients
Condition: Kidney Transplantation
Study type: Interventional
Phase: Phase 2

Summary: 
      Patients with renal failure need chronic dialysis or a kidney transplant to survive. Most
      kidney transplant patients must take medicines indefinitely to prevent their immune systems
      from rejecting the kidney. Long-term exposure to these anti-rejection medicines can damage
      the transplanted kidney.

      The purpose of this study is to determine whether giving patients cells from the donor's bone
      marrow will reduce or eliminate the need for long-term use of these anti-rejection drugs. In
      addition to the donor's bone marrow cells, patients will receive the drugs thymoglobulin and
      sirolimus.

      A total of 20 patients will participate in this five-year study.
    

Detailed description: 
      This protocol will evaluate the combination of Thymoglobulin (Sangstat), sirolimus and donor
      bone marrow infusion for its ability to induce a state of donor specific hematopoietic
      chimerism and immune hyporesponsiveness within the context of renal transplantation.
      Thymoglobulin (Sangstat), a FDA-approved polyclonal rabbit-IgG antithymocyte preparation,
      will be given for up to ten days at the time of transplantation to effect lymphocyte
      depletion. This will be combined with sirolimus (rapamycin, Wyeth-Ayerst), an oral
      immunosuppressant agent recently approved by the FDA. Sirolimus allows for antigen specific T
      cell activation but prevents T cell clonal expansion by interrupting IL-2 receptor beta-chain
      signal transduction. Donor bone marrow will be administered seven days following transplant.
      Patients demonstrating six months of rejection free graft survival will have their sirolimus
      withdrawn over three months beginning at the sixth month anniversary of the transplant.

      Twenty people will be evaluated in this pilot protocol. Approximately ten will receive living
      donor kidney allografts and the remaining patients will receive cadaveric kidney allografts.
      Patients will be treated with Thymoglobulin beginning prior to graft implantation and
      continuing for approximately ten days. Glucocorticosteroids will be given during the first
      Thymoglobulin treatment to limit monocyte activation and prevent the cytokine release
      syndrome associated with the initial administration of this antibody preparation. Patients
      will be given sirolimus orally beginning the day after transplantation and continuously
      thereafter. Donor bone marrow will be administered seven days following transplantation.
      Patients will then be monitored for evidence of allograft rejection using standard functional
      parameters and protocol allograft biopsies. In addition, patients will be followed for
      specific desired effects, including a transient state of donor hematopoietic mixed
      microchimerism and allospecific AICD. Both of these are expected to promote the development
      of allospecific graft tolerance. This will be accomplished by assaying peripheral blood and
      allograft biopsies for apoptosis and the peripheral blood for evidence of alloreactive T cell
      clone depletion and donor chimerism.
    

Intervention name(s): Allogeneic Bone Marrow, Anti-Thymocyte Globulin (Sangstat) & Sirolimus (Wyeth-Ay
Intervention type(s): Drug
Intervention MeSH terms: Sirolimus; Antilymphocyte Serum
Primary purpose: Treatment
Keywords: Immunosuppression; Transplant; Kidney Transplant