The Use of Campath-1H, Tacrolimus, and Sirolimus Followed by Sirolimus Withdrawal in Renal Transplant Patients

Drugs that suppress the immune system, such as sirolimus and tacrolimus, have contributed to increased success of transplantation. However, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs make patients more susceptible to infection, endangering their health and survival. Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. This study will determine the effects of intravenous alemtuzumab and oral sirolimus and tacrolimus after kidney transplantation. The study will also evaluate this regimen's potential to allow eventual discontinuation of components of long-term immunosuppressive therapy.

This study will last up to 4 years. Participants will undergo kidney transplantation on Day 0 and will receive intravenous doses of alemtuzumab, acetaminophen, and diphenhydramine on Days 0, 1, and 2, as well as methylprednisolone on Day 0. After transplant, patients will receive up to 10 days of valganciclovir or acyclovir. Participants will take tacrolimus daily by mouth for at least 60 days after transplant and sirolimus daily by mouth for at least 12 months after transplant. As part of opportunistic infection (OI) prophylaxis, participants will also take sulfamethoxazole-trimethoprim by mouth 3 times a week, valganciclovir or acyclovir for up to 10 days post-transplant, and clotrimazole or nystatin by mouth for at least 3 months post-transplant.

There will be a minimum of 62 study visits spread out over 4 years after transplant. Vital signs measurement, adverse event and OI reporting, medication history, physical exam, and blood collection will occur at selected visits. Sirolimus withdrawal will begin when a participant meets certain study criteria. The withdrawal process will occur over a minimum of 3 months at an approximate rate of 33% of the pre-withdrawal dose per month. Participants eligible for sirolimus withdrawal will undergo several kidney biopsies, including one 2 weeks prior to the start of withdrawal, 6 and 12 months after completion of withdrawal, 1 year after study enrollment, and annually thereafter.