Using Donor Stem Cells and Alemtuzumab to Prevent Organ Rejection in Kidney Transplant Patients
Condition: Kidney Transplantation; Kidney Disease; Kidney Failure
MeSH terms: Kidney Diseases; Renal Insufficiency
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Alemtuzumab is a man-made antibody used to treat certain blood disorders. This study will
      evaluate treatment of kidney transplant recipients with alemtuzumab and other immune system
      suppressing medications with or without infusions of bone marrow stem cells from the kidney
      donor. The purpose of this study is to find out which strategy is more effective in
      preventing organ rejection and maintaining patient health.
    

Detailed description: 
      Organ transplantation is a common procedure in hospitals, but organ rejection and serious
      side effects are potential problems for the patient. Mycophenolate mofetil, sirolimus, and
      tacrolimus are drugs used to decrease immune system activity in people who have received
      organ transplants so that the new organ will not be rejected. Alemtuzumab is a monoclonal
      antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients.
      In this study, alemtuzumab will be used to destroy the recipient's white blood cells (WBCs)
      at the time of transplantation. It is hoped that WBCs produced after alemtuzumab
      administration will recognize the transplanted liver as "self" and will not attack the new
      kidney.

      To further assist the immune system in accepting the donor kidney, some patients in this
      study will also receive two infusions of bone marrow stem cells from the kidney donor. Bone
      marrow stem cells are adult blood cells from which other specialized blood cells, such as T
      cells, develop. Treatment with these cells is believed to create a state of "chimerism" in
      the body, where the immune cells of both the donor and recipient can coexist and tolerate the
      presence of a donor organ. This study will evaluate the safety and effectiveness of an
      antirejection regimen including alemtuzumab and other immunosuppressive medications and donor
      bone marrow stem cell infusions in patients undergoing kidney transplantation.

      This study will last 3 years. Participants will be randomly assigned to receive either the
      full immunosuppressive therapy and donor bone marrow stem cell infusions (Group 1) or
      immunosuppressive therapy alone (Group 2). Patients will undergo kidney transplantation at
      the start of the study on Day 0. Patients will receive inpatient infusions of alemtuzumab on
      Days 0 and 4. Starting on Day 0, patients will begin taking mycophenolate mofetil; starting
      on Day 1, patients will also begin taking tacrolimus. On Day 5, patients in Group 1 will
      receive their first of 2 infusions of purified stem cells taken from the kidney donor's bone
      marrow; their second infusion of stem cells will occur sometime between Months 4 and 6
      post-transplant.

      Beginning between Months 4 and 6 post-transplant, all participants will begin receiving
      low-dose maintenance immunosuppressive therapy with sirolimus, as is typical for
      post-transplant antirejection therapy. One year post-transplant, patients will be evaluated
      for the potential to withdraw some or all of this maintenance immunotherapy. Participants
      will be monitored for 3 years post-transplant. Urine collection will occur at Week 1 and
      Months 1, 3, 6, and 9. At Months 12, 24, and 30, participants will undergo kidney biopsies.
      Blood collection will occur at regular intervals for laboratory tests to evaluate the immune
      system's response to the transplanted kidney.
    

Intervention name(s): Alemtuzumab; Mycophenolate mofetil; Sirolimus; Tacrolimus; Donor bone marrow stem cell infusion; Kidney transplant
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4; Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study; Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study; Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study; 2 doses of kidney donor's bone marrow stem cells by IV infusion on Day 5 and sometime between Months 4 and 6; Occurs at study entry
Other intervention name(s): Campath; Cellcept; rapamycin, Rapamune; FK-506
Intervention MeSH terms: Mycophenolic Acid; Sirolimus; Alemtuzumab; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: kidney; kidney transplant; kidney transplantation; transplant; transplantation; renal; renal transplant; renal transplantation; kidney disease; chronic; renal failure; kidney failure