Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation
| Status: | Completed |
|---|---|
| Conditions: | Orthopedic |
| Therapuetic Areas: | Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 9/8/2018 |
| Start Date: | February 2005 |
| End Date: | November 28, 2011 |
Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation
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.
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.
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.
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.
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
We found this trial at
1
site
1 Medical Center Blvd
Winston-Salem, North Carolina 27103
Winston-Salem, North Carolina 27103
(336) 716-2011
Wake Forest University Baptist Medical Center Welcome to Wake Forest Baptist Medical Center, a fully...
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