Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant
Condition: End-stage Renal Disease; Renal Transplantation; Kidney Transplantation
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will examine the safety and effectiveness of a combination kidney and bone marrow
      transplant from a relative with the same (or nearly the same) blood cell type as the
      transplant recipient. An investigational medication will be given prior to and after the
      transplant to help protect the transplanted kidney from attack by the body's immune system.
    

Detailed description: 
      Of the two currently available treatments for kidney failure, long-term dialysis and kidney
      transplantation, only kidney transplantation provides a potential cure. After a kidney
      transplant, the body's immune system recognizes the kidney as foreign and tries to attack and
      destroy it in a process called rejection. To avoid rejection, participants must take
      medications called immunosuppressants or anti-rejection drugs. It is believed that by
      transplanting bone marrow at the same time as a solid organ such as a kidney, a state of
      "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved.
      Mixed chimerism may prevent rejection without the need for anti-rejection drugs.

      Participants in this study will receive a simultaneous bone marrow and kidney transplant from
      the same living related donor in an attempt to establish mixed chimerism. Prior to
      transplantation, participants will undergo a "conditioning regimen" involving
      cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive
      medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a
      short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an
      investigational medication that has not been approved by the FDA. The primary goal of the
      study is to investigate the safety of the conditioning regimen and its ability to promote
      mixed chimerism so that the transplanted kidney is not destroyed. The study will also
      determine whether participants with mixed chimerism can eventually be safely removed from
      long-term immunosuppressive therapy following transplantation.

      Participants will be assessed before and after transplantation and will be followed ≤36
      months.
    

Intervention name(s): Conditioning Regimen
Intervention type(s): Drug
Intervention description(s): Cyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.
Other intervention name(s): nonmyeloablative preparative regimen
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: End-stage renal disease; Renal Transplant; Bone Marrow Transplant; nonmyeloablative conditioning regimen