Effectiveness of the Investigational Drug Campath-1H in Preventing Rejection of Transplanted Kidneys
Status:
Completed
Trial end date:
2008-06-01
Target enrollment:
Participant gender:
Summary
This protocol will test a humanized monoclonal antibody known as Campath-1H for its ability
to induce a state of permanent allograft acceptance, or tolerance, when administered in
combination with a brief course of the immunosuppressive drug deoxyspergualin (DSG) at the
time of human renal allotransplantation. Campath-1H is specific for the common lymphocyte and
monocyte antigen CD52. Its administration temporarily depletes mature lymphocytes and some
monocytes without altering neutrophils or hematopoietic stem cells. Deoxyspergualin inhibits
the NFkB pathway thus preventing monocyte and macrophage activation.
Recipients of living or cadaveric donor kidneys will be treated with one dose of Campath-1H
prior to transplantation to insure that peripheral depletion is achieved at the time of graft
reperfusion. Three subsequent doses of Campath-1H will be administered on the first, third
and fifth days after the transplant to deplete passenger donor leukocytes and residual
recipient cells that mobilize in response to the allograft. In addition, patients will be
treated with DSG for 14 days beginning on the day prior to surgery. This trial expands on
pilot studies at the NIH of 15 patients in which Campath was given alone at the time of
transplantation. In those studies, excellent peripheral depletion occurred after just one
dose of Campath though central depletion required additional dosing. This allowed for greatly
reduced immunosuppression to be used to prevent rejection, but to date, all patients have
required some immunosuppressive medication. It is hoped that the addition of DSG will
eliminate the need for long-term immunosuppression.
Patients will be followed closely in the post transplant period. If patients experience
rejection, they will be treated with methylprednisolone and have immunosuppression added
using sirolimus as the predominant immunosuppressive agent. In the previous phase of this
study without DSG, this maneuver has in all cases been successful in returning the allograft
to normal function.
In addition to evaluating graft function following transplantation, this protocol will also
characterize and evaluate the function of the immune system and the composition of the T cell
repertoire following the administration of Campath-1H and DSG, and during immune system
recovery after transplantation.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)