Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00331162
Status:
COMPLETED
Last Update Posted:
2018-09-06
First Post:
2006-05-26
Brief Title:
Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation
Sponsor:
Wake Forest University Health Sciences
Organization:
Wake Forest University Health Sciences
Study Overview
Official Title:
Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation
Status:
COMPLETED
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this research study is to compare the effects of the two most commonly used anti-T cell induction agentsalemtuzumab 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
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 p00078
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 kidneypancreas 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
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 p00078
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 kidneypancreas 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None