Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Immune Tolerance Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00078559

Purpose

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.

Condition	Intervention	Phase
Kidney Transplantation Kidney Disease	Drug: Alemtuzumab Drug: Sirolimus Drug: Tacrolimus Procedure: Kidney transplant	Phase I Phase II

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Sirolimus Tacrolimus anhydrous Tacrolimus Campath Alemtuzumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Campath-1H/Tacrolimus/Sirolimus Withdrawal in Renal Transplantation

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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 ]

Enrollment:	10
Study Start Date:	November 2003
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Alemtuzumab 30mg IV on days 0 (transplant), 1, and 2 Drug: Sirolimus 2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year Drug: Tacrolimus 2mg oral bid on days 1-60 Procedure: Kidney transplant Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)

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 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)
Receiving only a kidney and no other organs
Able to take medications by mouth
Willing to use acceptable methods of contraception

Exclusion Criteria

Received HLA-identical living-donor kidney transplant
HLA-antigen mismatch greater than 3
Panel reactive antibody (PRA) value greater than 10% at any time prior to enrollment
Received a non-heart-beating donor allograft
Received a kidney from a donor who is greater than 60 years of age
End-stage renal disease (ESRD) due to focal segmental glomulerosclerosis (FSGS)
Previous kidney transplant
Received multiorgan transplant
Concomitant systemic corticosteroid therapy for other medical diseases
Known hypersensitivity to alemtuzumab, tacrolimus, methylprednisolone, or sirolimus
HIV infected
Hepatitis C virus infected
Positive for hepatitis B surface antigen
Received dual or en-bloc pediatric kidneys
Anti-human globulin (AHG) or T cell crossmatch positive
Investigational drug within 6 weeks of study entry
Known clinically significant cardiovascular or cerebrovascular disease
Previous or current history of cancer or lymphoma. Patients with adequately treated basal or squamous cell skin carcinoma are not excluded.
Clinically significant coagulopathy or a requirement for chronic anti-coagulation therapy precluding biopsy
CMV-negative recipient, if received kidney is from a CMV-positive donor
History of a psychological illness or condition that, in the opinion of the investigator, may interfere with the study
Graves disease. Patients who have been previously adequately treated with radioiodine ablative therapy are not excluded.
Active systemic infections
Platelets less than 100,000 cells/mm3 at study entry
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078559

Locations

United States, Wisconsin
University of Wisconsin - Madison, Department of Surgery
Madison, Wisconsin, United States, 53792-1735

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network

Investigators

Principal Investigator:

Stuart Knechtle, MD

Immune Tolerance Network

More Information

Additional Information:

Click here for the Immune Tolerance Network Web site This link exits the ClinicalTrials.gov site

Publications:

First MR. Tacrolimus based immunosuppression. J Nephrol. 2004 Nov-Dec;17 Suppl 8:S25-31. Review.

Gourishankar S, Turner P, Halloran P. New developments in immunosuppressive therapy in renal transplantation. Expert Opin Biol Ther. 2002 Jun;2(5):483-501. Review.

Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53.

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	ITN013ST
Study First Received:	March 1, 2004
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00078559 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Immunosuppression
Renal Failure

Study placed in the following topic categories:

Sirolimus
Immunologic Factors
Clotrimazole
Miconazole
Tioconazole
Tacrolimus
Immunosuppressive Agents

Anti-Bacterial Agents
Urologic Diseases
Alemtuzumab
Antifungal Agents
Kidney Diseases
Kidney Failure

Additional relevant MeSH terms:

Sirolimus
Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Antibiotics, Antineoplastic
Immunosuppressive Agents

Pharmacologic Actions
Anti-Bacterial Agents
Urologic Diseases
Alemtuzumab
Therapeutic Uses
Antifungal Agents
Kidney Diseases

ClinicalTrials.gov processed this record on May 07, 2009