Cell Therapy for Immunomodulation in Kidney Transplantation

Study Overview
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Brief Summary
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This study investigates treatment with recipient regulatory T cells and donor bone marrow together with tocilizumab for immunomodulation in living donor kidney transplant recipients.

Official Title
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A Prospective Controlled Trial to Evaluate Safety and Efficacy of in Vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-mismatched Living Donor Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: Regulatory T cells
* Drug: Tocilizumab
* Other: Bone marrow
* Procedure: Kidney transplant
* Other: Immunosuppressive drug therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has provided written informed consent. Patient is 18 years or older. Patient is a planned recipient of a living donor kidney transplant. Patient is a planned recipient of an ABO blood group-compatible kidney graft. Patient is a planned recipient of a kidney graft from a donor that is not HLA (human leukocyte antigen)-identical. Patient is negative for DSA (donor-specific antibodies). WOCBP (women of child-bearing potential) must have a negative pregnancy test at inclusion. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized. Exclusion Criteria: Patient is EBV (epstein barr virus)-negative on serology. Patient is HIV-positive or suffering from chronic viral hepatitis. Patient is CMV (cytomegalo virus)-negative and receiving a kidney from a CMV-positive donor. Positive T-cell lymphocytotoxic cross match. Patient with prior kidney transplant or non-renal solid organ transplant. Patient has a known contraindication to any of the protocol-specified treatments. Patient had been diagnosed with a malignancy within 5 years prior to study entry, excluding non-metastatic basal or squamous cell carcinoma of the skin. Female patients who are breast-feeding. Female patients with a positive pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Treatment with regulatory T cells, donor bone marrow and tocilizumab in addition to immunosuppressive drug therapy in kidney transplant recipients | Other: Regulatory T cells<br>* Single infusion of expanded regulatory T cells.<br>Drug: Tocilizumab<br>* Treatment during first month post-transplant.<br>Other: Bone marrow<br>* Infusion of donor bone marrow cells.<br>Procedure: Kidney transplant<br>* Living donor kidney transplantation.<br>Other: Immunosuppressive drug therapy<br>* Immunosuppressive drug therapy.<br>|
| Active Comparator: Control group<br>Immunosuppressive drug therapy without treatment with regulatory T cells, donor bone marrow and tocilizumab in kidney transplant recipients | Procedure: Kidney transplant<br>* Living donor kidney transplantation.<br>Other: Immunosuppressive drug therapy<br>* Immunosuppressive drug therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured as GVHD (graft-versus-host disease), impaired graft function or patient death | Incidence of composite safety endpoint by 12 months post-transplant. | 12 months | 
| Chimerism | Total leukocyte donor chimerism in blood. | 1 month |