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Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients
This study is currently recruiting patients.
Sponsored by: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
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Information provided by: | Warren G Magnuson Clinical Center (CC) |
Purpose
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.
Condition | Treatment or Intervention | Phase |
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Kidney Transplantation |
Drug: Allogeneic Bone Marrow, Anti-Thymocyte Globulin (Sangstat) & Sirolimus (Wyeth-Ay |
Phase II |
MedlinePlus consumer health information
Study Type: Interventional
Study Design: Treatment, Safety/Efficacy
Official Title: Induction of Donor Specific Immunologic Hyporesponsiveness with Thymoglobulin, Sirolimus and Donor Bone Marrow Infusion
Expected Total Enrollment: 20
Study start: June 9, 2003
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.
The rationale for this combination is to 1) eliminate existing alloreactive T cell clones that could initiate a rejection at the time of transplantation using the T cell depleting properties of Thymoglobulin; 2) to create a milieu conducive for the induction of graft specific activation induced cell death (AICD) in repopulating T cells in the periphery and in the thymus such that an allospecific T cell deficit is induced; and 3) to establish a state of mixed allogeneic chimerism with donor bone marrow to promote the maintenance of allospecific hyporesponsiveness. The desired effect of this therapy is to induce a state of allospecific tolerance allowing for rejection-free graft survival without the chronic need for immunosuppressants, and to do so using a regimen that avoids most of the chronic drug toxicities inherent in the use of calcineurin inhibitors and glucocorticosteroids.
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.
Eligibility
Genders Eligible for Study: Both
Criteria
Location and Contact Information
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