Pharmacodynamics, Pharmacogenomics, and Preliminary Safety and Efficacy of Alemtuzumab Induction and Tacrolimus in Pediatric Intestinal Transplantation (IND # 100496)

Detailed Summary

This open-label clinical trial will evaluate the safety and efficacy of Alemtuzumab (Campath, Bayer Corp., Pittsburgh) in children (0-17) and adults (18-25) receiving intestinal transplant. Seventy-five subjects receiving primary or repeat intestine transplantation will be enrolled. Primary endpoints include the incidence and severity of biopsy-proven acute cellular rejection, the incidence of freedom from steroids at 5 years, and the incidence of subjects with steroid-free Tacrolimus at whole blood concentrations \< 10 ng/ml. Secondary endpoints include a) incidence and severity of opportunistic infections (CMV and EBV), post-transplant lymphoproliferative disorder (PTLD), and chronic rejection b) use of non-immunosuppressive co-medications, c) time to repopulation of all lymphocyte subsets, d) longitudinal characterization of donor-specific alloreactivity in mixed lymphocyte responses (MLR), to identify the time at which it decreases to a level less than third-party-specific alloreactivity e) longitudinal expression (mRNA) of genes, to identify rejection- and non-rejection-specific genes and f) characterization of whole genome mutations, which show differences in parent-to-child transmission between rejectors and non-rejectors. This will identify rejection- and non-rejection-specific genes bearing genetic variants, which might impact on gene function, and complement candidate gene identification efforts based on SNP transmission.

Study Details

Timeline

Interventions