Primary Outcome Measures:
- Incidence rate of acute rejection in all enrolled participants [ Time Frame: Transplantation to end of study ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Rate of acute rejection in all enrolled participants following sirolimus withdrawal [ Time Frame: transplantation to end of study ] [ Designated as safety issue: Yes ]
- acute rejection rate between initiation of sirolimus withdrawal and end of study [ Time Frame: initiation of sirolimus to end of study ] [ Designated as safety issue: Yes ]
- time from transplantation to acute rejection in participants for whom sirolimus withdrawal is not initiated [ Time Frame: transplantation to acute rejection ] [ Designated as safety issue: No ]
- time from transplantation to acute rejection in participants for whom acute rejection occurred in the 1 year post-transplant period [ Time Frame: Transplantation to acute rejection 1-year post-transplant ] [ Designated as safety issue: No ]
- time from transplantation to acute rejection in participants for whom sirolimus withdrawal has been initiated [ Time Frame: Transplantation to acute rejection ] [ Designated as safety issue: No ]
- incidence rate of death, graft loss, or severe acute rejection, stratified by sirolimus withdrawal status [ Time Frame: Transplantation to acute rejection ] [ Designated as safety issue: Yes ]
- incidence and severity of acute rejections, stratified by sirolimus withdrawal status [ Time Frame: Transplantation to acute rejection ] [ Designated as safety issue: Yes ]
- proportion of participants requiring anti-lymphocyte therapy (OKT3, ATG) for an acute rejection, stratified by sirolimus withdrawal status [ Time Frame: Transplantation to acute rejection ] [ Designated as safety issue: Yes ]
- safety, including incidence of post-transplant infections, malignancies, and side effects associated with conventional immunosuppression [ Time Frame: Transplantation to end of study ] [ Designated as safety issue: Yes ]
- renal function as measured by serum creatinine, stratified by sirolimus withdrawal status [ Time Frame: Transplantation to end of study ] [ Designated as safety issue: Yes ]
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 intravenous 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, IV 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.