Low Dose Sirolimus or CsA-Based Maintenance Immunosuppression After Induction With Campath-1 in Kidney Transplantation

NCT00309270 | Completed Phase 2

• 1 other identifier: CAMPATH
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Transplant

Keywords

Campath-1H, low-dose immunosuppression, T regulatives cells

Outcome Measures

Primary Outcomes (3)

• Time course of immunophenotyping and lymphocyte function assays in the two groups of kidney transplant recipients randomized to low-dose sirolimus or CsA- based maintenance immunosuppression after Campath-1H induction therapy

• Graft function and survival

• Safety of induction therapy with Campath-1H and low-dose maintenance immunosuppressive regimen

Interventions

Campath-1H DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible kidney transplant according to standard criteria
• Recipient of first kidney transplant
• Cadaver or living-related donor
• Written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Hospital "Ospedali Riuniti" of Bergamo

Bergamo, 24128, Italy

Location

MeSH Terms

Interventions

Alemtuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Norberto Perico, MD

  Mario Negri Institute for Pharmacological Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 30, 2006
• First Posted: March 31, 2006
• Study Start: February 1, 2003
• Study Completion: April 1, 2010
• Last Updated: May 22, 2006

Record last verified: 2006-03

Locations

IT (1)