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

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00331162
• Collaborator: (none)
• Enrollment: 222
• Location: 1
• Arms: 2
• Actual Duration (Months): 81.8
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Graft Rejection	Drug: Alemtuzumab; Drug: Anti-Thymocyte Globulin	Phase 4

Detailed Description

Anti-Thymocyte Globulin, rabbit (r-ATG, Thymoglobulin®) is a polyclonal antibody against T-lymphocytes that is used for the prevention and treatment of acute allograft rejection. r-ATG induction therapy is effective in preventing acute allograft rejection, however the usual 7-14 day course involves extensive clinical monitoring and is costly. Recent studies had suggested that smaller cumulative doses are efficacious for induction therapy, and may have an advantage by decreasing the adverse effects associated with the agent (such as leukopenia and thrombocytopenia). Our program subsequently modified our r-ATG induction regimen in November 2001 to give doses on alternate days for at least three doses and has achieved excellent results. However, this regimen is somewhat complex in that it requires central venous access for administration, pre-medication administration to prevent infusion-related reactions, and monitoring of vital signs during each infusion.

Alemtuzumab (Campath®) is a humanized monoclonal antibody to CD52 that is FDA approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), but has also been used for immunosuppression induction at the time of solid organ transplant and as anti-rejection therapy. CD52 is present on most lymphocytes, macrophages, monocytes, and NK cells, and causes antibody-dependent cell lysis following the binding of alemtuzumab to the CD52 surface antigen. Alemtuzumab produces significant lymphocyte depletion similar to r-ATG, so some investigators began evaluating it as a preconditioning agent in tolerance protocols (using very low-dose maintenance immunosuppression) in solid organ transplantation. While these studies showed no significant tolerogenic potential for alemtuzumab, one or two 20-30 mg doses of alemtuzumab produced a similar degree of lymphocyte depletion as r-ATG administration. Based on these preliminary data in transplant recipients and prior safety data obtained from safety and efficacy studies of alemtuzumab in patients with rheumatoid arthritis, some US transplant centers changed from using r-ATG to alemtuzumab as their primary induction agent. Most of these centers (notably Wisconsin and Northwestern, where more than 500 kidney and pancreas patients have received alemtuzumab, personal communication Dixon Kaufman, Northwestern) use one or two doses of alemtuzumab for induction, followed by a traditional 2-3 drug maintenance immunosuppressive regimen (rather than the low-dose immunosuppression used in the tolerance protocols).

Knechtle and colleagues from the University of Wisconsin have reported a comparable incidence of acute rejection and favorable graft survival in 130 patients who received a single intraoperative 30 mg dose (+/- an additional dose on post-operative day 1) of alemtuzumab compared with a historical cohort who received r-ATG, OKT3, an IL-2 receptor antagonist, or no induction. In addition, the group found that there was a dramatically lower incidence of acute rejection in the patients who experienced delayed graft function in the alemtuzumab group (9% vs 45% in the control group, p=0.0078).

The use of alemtuzumab as an induction agent in solid organ transplantation is appealing. Only a single intraoperative dose would be required (compared with between 2 and 6 additional doses of r-ATG post-op), thereby eliminating the necessity for central venous access and extensive clinical and nurse monitoring. In addition, the cost of therapy would be less with alemtuzumab than with r-ATG. At WFUBMC, 18 recipients of kidney or kidney/pancreas transplants who received alemtuzumab have had only a 9% six-month rejection rate. Our clinical experience suggests that the agents produce similar results; however, a prospective, randomized study to compare the safety and efficacy of alemtuzumab with r-ATG has not been reported. Also, although alemtuzumab would offer a significant medication cost savings over r-ATG, the impact on the overall cost of care has yet to be established. A comparative study will help us decide if we should make alemtuzumab our new standard of care at this institution.

The purpose of this study is to evaluate the use of alemtuzumab (Campath-1H) for induction therapy in kidney and pancreas transplantation compared to our standard of care, alternate-day r-ATG.

Study Design

• Study Type: Interventional
• Actual Enrollment: 222 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation
• Actual Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Nov 28, 2011
• Actual Study Completion Date: Nov 28, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Patient Survival [5 years]

   The number of patients that survived after transplantation occurred was reported.

2. Graft Survival [5 years]

   The number of patients with graft survival after kidney alone, simultaneous pancreas-kidney (SPK), and pancreas after kidney (PAK) transplant.

3. Acute Rejection [5 years]

   The number of patients with acute rejection after transplantation was reported.

Secondary Outcome Measures

1. Hematologic Adverse Events [2 years]

2. Infectious Adverse Events [2 years]

   Number of events for infectious adverse events were reported (Polyoma virus nephropathy (PVD), cytomegalovirus (CMV), bacterial and fungal infections).

3. Other Adverse Events [2 years]

   Number of patients with other adverse events (posttransplant lymphoproliferative disorder (PTLD), and nonskin malignancy), were reported.

4. Cost [2 years]

5. Health Status and Quality of Life [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: Alan C Farney, MD, Ph.D., Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

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.
• 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.
• 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.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00331162
• Other Study ID Numbers: BG04-498
• First Posted: May 29, 2006
• Last Update Posted: Sep 6, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Renal Transplantation; Pancreas Transplantation; Graft Rejection; Immunosuppression; Kidney failure, chronic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2
• Additional relevant MeSH terms: Alemtuzumab; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Period Title: Overall Study
STARTED	113	109
COMPLETED	113	109
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin	Total
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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	Total of all reporting groups
Overall Participants	113	109	222
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (12)	49 (13)	50 (12)
Sex: Female, Male (Count of Participants)
Female	46 40.7%	47 43.1%	93 41.9%
Male	67 59.3%	62 56.9%	129 58.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	34 30.1%	36 33%	70 31.5%
White	74 65.5%	69 63.3%	143 64.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 4.4%	4 3.7%	9 4.1%

Outcome Measures

1. Primary Outcome

Title	Patient Survival
Description	The number of patients that survived after transplantation occurred was reported.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	113	109
Count of Participants [Participants]	109 96.5%	104 95.4%

2. Primary Outcome

Title	Graft Survival
Description	The number of patients with graft survival after kidney alone, simultaneous pancreas-kidney (SPK), and pancreas after kidney (PAK) transplant.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Number the analyzed in one or more rows differs from overall number analyzed because there were subgroups for transplantation.

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	113	109
Kidney alone	78 69%	84 77.1%
SPK	21 18.6%	13 11.9%
PAK	4 3.5%	0 0%

3. Primary Outcome

Title	Acute Rejection
Description	The number of patients with acute rejection after transplantation was reported.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	113	109
Count of Participants [Participants]	16 14.2%	28 25.7%

4. Secondary Outcome

Title	Hematologic Adverse Events
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No data was collected

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	0	0

5. Secondary Outcome

Title	Infectious Adverse Events
Description	Number of events for infectious adverse events were reported (Polyoma virus nephropathy (PVD), cytomegalovirus (CMV), bacterial and fungal infections).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	113	109
CMV	9	18
PVN	1	8
Fungal infections	11	11
Bacterial Infections	89	92

6. Secondary Outcome

Title	Other Adverse Events
Description	Number of patients with other adverse events (posttransplant lymphoproliferative disorder (PTLD), and nonskin malignancy), were reported.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	113	109
PTLD	0 0%	1 0.9%
Other Nonskin Malignancy	0 0%	2 1.8%

7. Secondary Outcome

Title	Cost
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No data was collected

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	0	0

8. Secondary Outcome

Title	Health Status and Quality of Life
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

No data was collected.

Arm/Group Title	Alemtuzumab	Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.	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
Measure Participants	0	0

Adverse Events

Time Frame	5 years
Arm/Group Title	Alemtuzumab		Anti-Thymocyte Globulin
Arm/Group Description	Alemtuzumab: 30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.		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
All Cause Mortality
	Alemtuzumab		Anti-Thymocyte Globulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/113 (3.5%)		5/109 (4.6%)
Serious Adverse Events
	Alemtuzumab		Anti-Thymocyte Globulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/113 (9.7%)		44/109 (40.4%)
Blood and lymphatic system disorders
Pulmonary Embolism	0/113 (0%)		1/109 (0.9%)
Posttransplant lymphoproliferative disorder	0/113 (0%)		1/109 (0.9%)
Other (nonskin) Malignancy	0/113 (0%)		2/109 (1.8%)
Cardiac disorders
Cardiovascular Disease	2/113 (1.8%)		2/109 (1.8%)
Infections and infestations
Fungal Infection	11/113 (9.7%)		11/109 (10.1%)
Viral Infections	10/113 (8.8%)		27/109 (24.8%)
Renal and urinary disorders
Renal Allograft Pseudoaneurysm	1/113 (0.9%)		0/109 (0%)
Other (Not Including Serious) Adverse Events
	Alemtuzumab		Anti-Thymocyte Globulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/113 (0%)		0/109 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.