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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Treatments: Alemtuzumab; Sirolimus

Criteria

Inclusion Criteria:

• Eligible kidney transplant according to standard criteria

• Recipient of first kidney transplant

• Cadaver or living-related donor

• Written informed consent

Exclusion Criteria:

• Panel reactive antibodies titer >50%

• HLA identical

• High risk of recurrence of renal disease (FSGS, vasculitis, membranous nephropathy)

• Primary and secondary hyperlipidemia

• Platelet count <150000/microliter

• Specific contraindication to the study drug