MSC and Kidney Transplant Tolerance (Phase A)

Study Overview
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Brief Summary
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The general aim of the present study is to test a cell therapy with third-party ex-vivo expanded bone marrow-derived mesenchymal stromal cells (MSCs) as a strategy to induce tolerance in kidney transplant recipients with a deceased donor. MSCs will be prepared accordingly to established protocols, starting from the remnants in the bag and filter at the end of the bone marrow infusions. From these samples, MSCs will be expanded in good manufacturing practice (GMP) approved facilities and used for the present study in patients undergoing kidney transplantation. The proposed study will be developed in two phases: i) a pilot explorative safety/biologic-mechanistic phase (Phase A), ii) a pilot efficacy phase (Phase B).

Official Title
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Third-party Bone Marrow-derived Mesenchymal Stromal Cells to Induce Tolerance in Recipients of Kidney Transplants From Deceased Donors (Phase A)

Conditions
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Chronic Renal Failure

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First single kidney transplant; Capable of understanding the purpose and risk of the study; Written informed consent. Exclusion Criteria: PRA >10%; Specific contraindication to MSC infusion; Any clinical relevant condition that might affect study participation and/or study results; Childbearing potential without effective contraception; Pregnant women and nursing mothers; Unwillingness or inability to follow study protocol in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stromal Cells (MSC)<br>A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party (from healthy donors) MSCs will be performed in patients randomized to the MSC procedure in addition to the kidney transplantation. | Biological: Mesenchymal Stromal Cells<br> <br> |
| No Intervention: No intervention<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded. | Changes from baseline through study completion, up to 12 months after transplant. | 
| Circulating naive and memory T cell count (CD45RA/CD45RO) (flow cytometry analysis) |  | Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant. | 
| Circulating regulatory T cell count. |  | Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant. | 
| T-cell function in mixed lymphocyte reaction. | IFNg-producing T cells (spots/300.000 cells) and CD8+ T cell-mediated cytotoxicity (percentage of specific lysis) will be measured in mixed lymphocyte reaction. | Changes from baseline at 6 and 12 months after transplant. | 
| Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR |  | Changes from baseline at 6 and 12 months after transplant. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stromal cells, kidney transplantation, tolerance