Low Dose Sirolimus or CsA-Based Maintenance Immunosuppression After Induction With Campath-1 in Kidney Transplantation
Status:
Completed
Trial end date:
2010-04-01
Target enrollment:
Participant gender:
Summary
During the past 15 years, however, the superior immunosuppressive efficacy of CsA and the
well-known toxicity of long-term steroid therapy have prompted trials of steroid withdrawal
from renal allograft recipients at various intervals after transplantation. Steroid
withdrawal or avoidance must be balanced against the associated risk of precipitating acute
allograft rejection. Moreover, with the current immunosuppressive regimens, by 10 years
approximately 50% of grafts will have been lost due mainly to chronic rejection or the
side-effects of immunosuppressive therapy. Thus, the quest for therapies that might induce
specific immune tolerance - ideally via short-term interventions that would target only the
pathogenic immune response and leave the protective host immune response unimpaired - has
provided a "holy grail" for transplant immunologists.
The humanized IgG monoclonal antibody Campath-1H has been hypothesized to provide enough
immunosuppression that would allow maintenance therapy with low-dose CsA, and possibly
reprogramming the immune system so to encourage tolerance processes. Despite Campath-1H
immunosuppressive regimens have been claimed to induce a condition of "almost tolerance",
this has not been proved nor evidence of development of persistent regulatory immune
responses long-term post transplant has been provided. Thus, characterizing phenotypically
and functionally distinct subsets of T-regulatory cells possibly generated selectively in
non-rejecting transplant recipients in Campath-1H-based immunosuppressive regimens may help
to find new noninvasive markers of immune system activation to tailor immunosuppressive
protocols.
The primary aim of the study is to compare the effect of Campath-1H, low dose sirolimus
versus Campath-1H, low dose CsA, both in addition to low dose MMF on phenotypic and
functional profiles of peripheral blood mononuclear cells (PBMCs) in kidney transplant
recipients in a steroid-free regimen.
Phase:
Phase 2
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research