ACCEPTOR Kidney Transplant Study Opens for Enrollment

January 6, 2014 -- 

The ITN’s ACCEPTOR study (Post-transplant Cyclophosphamide) in kidney transplant is now open for enrollment at Johns Hopkins University.  The ACCEPTOR study, led by Lode Swinnen, MD, Ephraim Fuchs, MD, and Robert Montgomery, MD (Johns Hopkins Hospital) will combine hematopoietic stem cell (HSC) and kidney transplants as a means to potentially promote tolerance to the donor kidney.  

This approach to solid organ transplant aims to induce the stable presence of both host and donor immune systems simultaneously, called “mixed chimerism,” via HSC transplant. A chimeric immune system, even just temporarily, may create a more suitable environment for engraftment of the donor kidney and promote tolerance.  A similar approach using transient mixed chimerism has demonstrated some success in a few small studies including the ITN’s Mixed Chimerism trial in which 5 of the original 10 patients remain off immunosuppression, some for over 10 years (update of the study reported in the New England Journal of Medicine).  One of the aims of the ACCEPTOR study is to examine whether more durable mixed chimerism will be more effective for tolerance induction.

Mixed chimerism approaches for transplant tolerance are complicated by the possibility of graft-vs-host disease (GVHD) which arises from an immune attack by donor lymphocytes (from the HSC transplant) on normal recipient tissue. A key component of the ACCEPTOR study is high-dose cyclophosphamide, given on day 3 and day 4 post-transplant, which eliminates proliferating T cells from both donor and recipient while allowing other cyclophosphamide-resistant lymphocytes to re-populate. This regimen has demonstrated clinical success in reducing the incidence and severity of GVHD in HSC transplant recipients with hematologic disorders, and may also be a strategy to promote tolerance to the kidney.

The ACCEPTOR study will assess the safety of this regimen in 6 patients. Eligible participants will be weaned from immunosuppression in stages beginning at 6 months post-transplant and will be assessed for sustained allograft tolerance 52 weeks after completion of immunosuppression withdrawal.