Mesenchymal Stem Cells Under Basiliximab/Low Dose RATG to Induce Renal Transplant Tolerance
Status:
Terminated
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
This a pilot, explorative study to define the safety and biological/mechanistic effect of the
systemic intravenous infusion of syngeneic ex-vivo expanded MSCs in living-related kidney
transplant recipients (one or two HLA haplotype mismatches) under basiliximab/low-dose RATG
induction therapy and maintenance immunosuppressive drugs with the ultimate objective to test
the feasibility of safely achieving graft tolerance in a subsequent efficacy pilot study.
Specific objectives To compare changes in the immunophenotype and ex-vivo T-cell functional
tests from samples of peripheral blood and measurement in the urine of messenger RNA for
FoxP3,in kidney transplant recipients given or not syngeneic (from the recipient) MSC
infusion under basiliximab/low-dose RATG induction therapy and maintenance immunosuppressive
treatment with low-dose cyclosporine (CsA) plus low-dose mycophenolate mofetil (MMF).
This will assess at different time up to 12 months post transplant. In addition the safety
profile of MSC infusion will be investigated. We have planned to start with the safety and
biological/mechanistic study in 6 living-related kidney transplant recipients. Three patients
will receive ex-vivo expanded syngeneic MSC infusion (2x106 MSCs per kilogram body weight) at
the time of kidney transplant, and 3 additional patients no cells (controls), both under the
cover of induction therapy with basiliximab and low-dose RATG, and maintenance
immunosuppression with low-dose CsA and MMF. Randomization to MSC or no cell infusion will be
performed at the time the recipient will sign the informed consent to participate to the
study.
Should this biological/mechanistic ex vivo studies document that MSC infusion allows the
development of an immune microenvironment permissive to graft tolerance, a pilot efficacy
study to achieve operational tolerance after complete withdrawal of maintenance
immunosuppressive therapy will follow.
In this additional pilot explorative efficacy study all consecutive patients will be included
and followed until the first episode of rejection (if any) will occur or 29 consecutive
patients have successfully withdrawn the immunosuppressive therapy. This has been estimated
according to the Simon's two-stage minimax design.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research