Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation - Full Text View

Sponsor:	Wake Forest University Baptist Medical Center
Information provided by:	Wake Forest University Baptist Medical Center
ClinicalTrials.gov Identifier:	NCT00331162

Purpose

The purpose of this research study is to compare the effects of the two most commonly used anti-T cell induction agents(alemtuzumab and rabbit anti-thymocyte globulin) to prevent rejection in kidney and pancreas transplant patients. Alemtuzumab is Food and Drug Administration (FDA) approved for treating a certain type of cancer (leukemia), and Thymoglobulin® (rabbit anti-thymocyte globulin) is approved for anti-rejection treatment, but neither drug is FDA approved for administration at the time of transplantation to help prevent rejection. Even so, many transplant centers use these medications at the time of transplantation and believe that their use helps to decrease the risk of developing rejection following kidney and pancreas transplantation. Which drug might be better is not known. Subjects will receive either alemtuzumab (one administration) or rabbit anti-thymocyte (3 to 7 doses) at and within the first week of transplantation. Subjects will be assigned to either the alemtuzumab or rabbit anti-thymocyte globulin groups by chance. The two groups will be compared to see if there are meaningful differences for survival, organ function, side effects, and quality of life. The follow-up care after transplant for subjects in the study is the same as that for patients who are not in the study, except that a quality of life questionnaire (estimated to take 10 minutes to complete) will be completed at the time of transplant and through year 2 during selected scheduled clinic visits. A retrospective chart review will occur at 3-5 years post-transplant to follow incidence of chronic rejection, patient and graft survival and graft function.

Condition	Intervention	Phase
Graft Rejection	Drug: Alemtuzumab Drug: Anti-Thymocyte Globulin	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Pancreas Transplantation

Drug Information available for: Pancrelipase Campath Alemtuzumab Ultrase

U.S. FDA Resources

Further study details as provided by Wake Forest University Baptist Medical Center:

Primary Outcome Measures:

Patient survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Graft survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Acute Rejection [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Hematologic adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Infectious adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Other adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Cost [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Health status and quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	275
Study Start Date:	February 2005
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Alemtuzumab	Drug: Alemtuzumab 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.
Active Comparator: 2 Anti-Thymocyte Globulin	Drug: Anti-Thymocyte Globulin 1.5 mg/kg per dose through a central line intraoperatively and on POD# 2 and 4, then continue on alternate days until a therapeutic tacrolimus(or cyclosporine) level is achieved, or until the SCr < 3-4 mg/dL. Give first dose over 6 hours, subsequent doses over 4 hours. Premedication to be given with the first 3 doses: Tylenol 650mg PO/PR Benadryl 25-50mg PO/IV Daily scheduled corticosteroid dose or other corticosteroid as deemed appropriate. Hold infusion if temperature > 100.5ºF; Adjust dose for low WBC or Plt count Peripheral Thymoglobulin administration: Prepare dose in 500cc NS; Add heparin 1,000 units and hydrocortisone 20mg to the bag; Infuse over a minimum of 6 hours

Arms

Assigned Interventions

Active Comparator: 1

Alemtuzumab

Drug: Alemtuzumab

30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.

Active Comparator: 2

Anti-Thymocyte Globulin

Drug: Anti-Thymocyte Globulin

1.5 mg/kg per dose through a central line intraoperatively and on POD# 2 and 4, then continue on alternate days until a therapeutic tacrolimus(or cyclosporine) level is achieved, or until the SCr < 3-4 mg/dL.

Give first dose over 6 hours, subsequent doses over 4 hours.

Premedication to be given with the first 3 doses:

Tylenol 650mg PO/PR Benadryl 25-50mg PO/IV Daily scheduled corticosteroid dose or other corticosteroid as deemed appropriate.

Hold infusion if temperature > 100.5ºF; Adjust dose for low WBC or Plt count Peripheral Thymoglobulin administration: Prepare dose in 500cc NS; Add heparin 1,000 units and hydrocortisone 20mg to the bag; Infuse over a minimum of 6 hours

Show Detailed Description

Eligibility

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

Criteria

Enrollment of kidney transplant patients has been completed. The protocol has been amended to enroll 50 additional subjects who will receive either a simultaneous pancreas and kidney transplant, pancreas after kidney transplant, or solitary pancreas transplant.

Inclusion Criteria:

Male or female patients who receive a simultaneous pancreas and kidney transplant, pancreas after kidney transplant, or solitary pancreas transplant
Age 18 to 65
Females of child bearing potential must have a negative pregnancy test at time of transplant
Ability to give informed consent

Exclusion Criteria:

Inability to give informed consent
ABO incompatibility
T-cell or B-cell positive cross match
Patients with a previous hypersensitivity to alemtuzumab, anti-thymocyte globulin, or any monoclonal or polyclonal antibody preparation
Current active infection (currently receiving antibiotics, treatment for active infection within 1 week of transplant, or medical judgement)
Hepatitis B surface antigen positive
Human immunodeficiency virus positive
Any malignancy within 2 years except for successfully treated basal or squamous cell carcinoma of skin
Pregnancy
Breast feeding women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00331162

Locations

United States, North Carolina
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157

Sponsors and Collaborators

Wake Forest University Baptist Medical Center

Investigators

Principal Investigator:

Alan C Farney, MD, Ph.D.

Wake Forest University Baptist Medical Center

More Information

Publications:

Brennan DC, Flavin K, Lowell JA, Howard TK, Shenoy S, Burgess S, Dolan S, Kano JM, Mahon M, Schnitzler MA, Woodward R, Irish W, Singer GG. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation. 1999 Apr 15;67(7):1011-8. Erratum in: Transplantation 1999 May 27;67(10):1386.

Knechtle SJ, Pirsch JD, H Fechner J Jr, Becker BN, Friedl A, Colvin RB, Lebeck LK, Chin LT, Becker YT, Odorico JS, D'Alessandro AM, Kalayoglu M, Hamawy MM, Hu H, Bloom DD, Sollinger HW. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant. 2003 Jun;3(6):722-30.

Kaufman DB, Leventhal JR, Gallon LG, Parker MA. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results. Am J Transplant. 2006 Feb;6(2):331-9.

Responsible Party:	Alan Farney/Associate Professor, Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:	NCT00331162 History of Changes
Other Study ID Numbers:	BG04-498
Study First Received:	May 26, 2006
Last Updated:	January 10, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Wake Forest University Baptist Medical Center:

Renal Transplantation
Pancreas Transplantation
Graft Rejection
Immunosuppression

Kidney failure, chronic
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2

Additional relevant MeSH terms:

Antilymphocyte Serum
Campath 1G
Antibodies, Neoplasm
Pancrelipase
Alemtuzumab
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012