Clinical trial NCT00078559
Conditions: Kidney Transplantation Kidney Disease
Keywords: Immunosuppression Renal Failure
Sponsor: University of Wisconsin, Madison
Start date: 2003-11-01; Completion date: 2010-02-01
Enrollment: 10 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Transplant rejection occurs when a patient's body does not recognize the new organ and attacks it. Patients who have kidney transplants must take drugs to prevent transplant rejection. Alemtuzumab is a man-made antibody used to treat certain blood disorders. The purpose of this study is to test the safety and effectiveness of using alemtuzumab in combination with two other drugs, sirolimus and tacrolimus, to prevent organ rejection after kidney transplantation. This study will also test whether this combination of medications will allow patients to eventually stop taking antirejection medications entirely.

Study hypothesis: A new strategy of immunosuppression using alemtuzumab, tacrolimus, and sirolimus for human renal transplantation will permit a step-wise withdrawal from immunosuppressive drugs.

Detailed description:
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 Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed.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.

Arms: arm 1: None
Interventions: intervention 1: Alemtuzumab intervention 2: Sirolimus intervention 3: Tacrolimus intervention 4: Kidney transplant intervention 5: Methylprednisolone (or equivalent) intervention 6: Acetaminophen intervention 7: Diphenhydramine intervention 8: Trimethoprim (TMP)/Sulfa (Bactrim, Septra) intervention 9: Valgancyclovir intervention 10: Acyclovir intervention 11: Pentamidine intervention 12: Clotrimazole intervention 13: Nystatin
Intervention descriptions: intervention 1: 30mg intravenous infusion on days 0 (transplant), 1, and 2 intervention 2: 2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year intervention 3: 2mg orally twice daily, on days 1-60 intervention 4: Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch) intervention 5: 250 mg intravenous infusion 60 minutes prior to first dose of alemtuzumab intervention 6: 650 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis intervention 7: 25 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis intervention 8: 1 double strength tablet 3 times a week from day 1 through 1 year post-transplant. intervention 9: Given orally beginning on day 1 for up to 10 days post-transplant (until participant discharged from hospital if prior to 10 days). Dose adjusted based on participants calculated creatinine clearance intervention 10: 400 mg orally twice daily or 800 mg orally four times daily (dose adjusted based on calculated creatinine clearance and cytomegalovirus antibody serologic status of donor and recipient) for a minimum of 3 months starting when valganciclovir discontinued. intervention 11: 300 mg/6 mL inhalation therapy once monthly for a total of 6 treatments. First treatment given within one week post-transplant for participants with a known allergy or intolerance to sulfa intervention 12: 10 mg orally four times daily for a minimum of 3 months post-transplant (subjects take either clotrimazole or nystatin, not both) intervention 13: 500,000 units/5 mL orally four times daily for a minimum of 3 months post-transplant (subjects take either nystatin or clotrimazole, not both)

Protocol documents: