Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
Condition: Kidney Transplantation; Kidney Failure, Chronic
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 2

Summary: 
      In small initial studies, combined kidney and bone marrow transplants from the same donor
      have permitted some individuals to stop taking anti-rejection medicines without rejecting
      their transplant. This clinical trial will study this method in a greater number of people to
      determine if it is indeed effective and safe.
    

Detailed description: 
      All patients receiving an organ or tissue transplant must take special medicines known as
      "immunosuppressive drugs" in order to prevent the immune system from rejecting the
      transplant. These drugs can be very effective, but they leave the patient at an increased
      risk of serious infections and certain types of cancer. New methods of preventing transplant
      rejection are needed.

      Researchers have found that transplanting both bone marrow and a kidney from the same donor
      can create what is called "mixed chimerism." This means that the transplant recipient has a
      mixture of the donor and recipient's immune systems. It is believed that this mixture of
      immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney
      transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients
      to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This
      clinical trial will study more patients to confirm if the technique is safe and effective.

      Patients eligible for this study must be candidates for a living kidney transplant, and have
      an eligible donor identified. The transplant recipient and donor must both consent to
      participate in this study. Transplant recipients enrolled in the study will receive both
      kidney and bone marrow transplants from the same living donor. Prior to the transplant
      procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their
      immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a
      combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications
      called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been
      approved by the FDA. After the transplant procedure, transplant recipients will be prescribed
      steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the
      immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and
      kidney function meet certain criteria.

      Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the
      transplant procedure. After the transplant, patients will remain in the hospital until the
      doctor feels they are well enough to go home. Recipients will receive approximately monthly
      checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5
      years after transplant. Checkups will include physical exams, and blood and urine tests to
      assess immune system and kidney function. At four of these checkups, a kidney biopsy will be
      requested.

      Transplant donors enrolled in the study will attend a screening visit, which will include a
      physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital
      for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant
      donors may be asked at a later date to donate additional blood samples for research purposes.
    

Intervention name(s): Kidney Transplantation; Bone marrow transplantation; MEDI-507; cyclophosphamide; rituximab; Tacrolimus; corticosteroids; thymic irradiation
Intervention type(s): Procedure; Procedure; Biological; Drug; Biological; Drug; Drug; Radiation
Intervention description(s): Surgical transplantation of donor kidney; During kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone; 0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1; 60 mg/kg infusion on days -5, -4; 375 mg/m^2 infusion on days -7, -2, 5, and 12; 0.05 mg/kg intravenously twice daily starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56; 2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20; 700 cGy of thymic irradiation administered in a single dose on day -1
Other intervention name(s): Renal Transplantation; siplizumab; anti-CD2 monoclonal antibody; Cytoxan; Rituxan; PROGRAF®; methylprednisolone; prednisone
Intervention MeSH terms: Prednisone; Methylprednisolone; Cyclophosphamide; Rituximab; Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: renal allograft tolerance; mixed chimerism; kidney transplant; bone marrow transplant; antirejection; immunosuppression