- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00331162
Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation
Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
North Carolina
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Baptist Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
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
|
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient Survival
Time Frame: 5 years
|
The number of patients that survived after transplantation occurred was reported.
|
5 years
|
Graft Survival
Time Frame: 5 years
|
The number of patients with graft survival after kidney alone, simultaneous pancreas-kidney (SPK), and pancreas after kidney (PAK) transplant.
|
5 years
|
Acute Rejection
Time Frame: 5 years
|
The number of patients with acute rejection after transplantation was reported.
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hematologic Adverse Events
Time Frame: 2 years
|
2 years
|
|
Infectious Adverse Events
Time Frame: 2 years
|
Number of events for infectious adverse events were reported (Polyoma virus nephropathy (PVD), cytomegalovirus (CMV), bacterial and fungal infections).
|
2 years
|
Other Adverse Events
Time Frame: 2 years
|
Number of patients with other adverse events (posttransplant lymphoproliferative disorder (PTLD), and nonskin malignancy), were reported.
|
2 years
|
Cost
Time Frame: 2 years
|
2 years
|
|
Health Status and Quality of Life
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Alan C Farney, MD, Ph.D., Wake Forest University Health Sciences
Publications and helpful links
General 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. doi: 10.1097/00007890-199904150-00013. 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. doi: 10.1034/j.1600-6143.2003.00120.x.
- 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. doi: 10.1111/j.1600-6143.2005.01166.x.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BG04-498
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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