Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection

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.

Inclusion Criteria:

- Awaiting first or second transplant with a living donor or first transplant with a
cadaveric donor

- For living-donor transplants, must have one or more HLA antigen-mismatched donors
identified

- Serologic evidence of prior exposure to Epstein-Barr virus (EBV)

Exclusion Criteria:

- ABO blood group-incompatibility for a kidney graft of tissue from a donor

- Decreased circulating white blood cell count

- Positive for HIV-1, hepatitis B and C viruses

- Have had prior radiation therapy that could limit dose

- Lung capacity <50% of predicted normal

- Evidence of insufficient cardiac capacity

- Unwilling to use adequate contraception until 2 years after transplant

- Lactation or pregnancy

- Presence of antibody against the donor