Mesenchymal Stem Cells Under Basiliximab/Low Dose RATG to Induce Renal Transplant Tolerance

• Status: Terminated
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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and followed until the first episode of rejection (if any) will occur or 29 consecutive patients have successfully withdrawn the immunosuppressive therapy.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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Treatments: Antibodies, Monoclonal; Basiliximab; Cyclosporine; Cyclosporins; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Mycophenolate mofetil; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Thymoglobulin

Criteria

Inclusion Criteria:

• Male and female patients

• Aged 18 or older

• Non-HLA identical with the donor (one or two haplotype mismatches)

• First kidney transplant

• Capable of understanding the purpose and risk of the study

• Written informed consent

Exclusion Criteria:

• MSC donor positive for HIV-1, HIV-2, HBV, HCV, Syphilis.

• Specific contraindication to MSC infusion

• Any clinical relevant condition that might affect study participation and/or study results

• Pregnant women and nursing mothers

• Unwillingness or inability to follow study protocol in the investigator's opinion