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Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation

Phase 4
18 Years
65 Years
Open (Enrolling)
Graft Rejection

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Trial Information

Alemtuzumab Versus Thymoglobulin Induction Therapy in Kidney and Pancreas Transplantation

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.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Patient survival

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

Alan C Farney, MD, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wake Forest University Baptist Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

February 2005

Completion Date:

June 2015

Related Keywords:

  • Graft Rejection
  • Renal Transplantation
  • Pancreas Transplantation
  • Graft Rejection
  • Immunosuppression
  • Kidney failure, chronic
  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus, Type 2



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