MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients

Study Overview
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Brief Summary
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A phase- I clinical trial to determine safety and feasibilty of intravenous administration of mitomycin C-treated donor peripheral blood mononuclear cells in patients with chronic kidney disease stage KDIGO 4 or 5 (i.e. GFR 15-30 mL/min or < 15 mL/min) who receive a kidney transplant from a living donor.

Official Title
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A Single-arm Phase-I Trial for the Determination of Safety and Feasibility of the Intravenous Administration of Mitomycin C-treated Donor Peripheral Blood Mononuclear Cells (MICs) for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1 Study)

Conditions
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Kidney Failure, Chronic

Intervention / Treatment
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* Biological: Mitomycin C-induced peripheral blood mononuclear cells (MICs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic kidney disease stage KDIGO 4 or 5 First kidney transplant from a living donor Age ≥ 18 years ABO compatible CDC-PRA < 20% No donor-specific antibodies Negative CDC and ELISA crossmatch Immunosuppression with cyclosporin A, EC-MPS and methylprednisolone Informed consent Adequate contraception (women with child bearing potential) Exclusion Criteria: Psychiatric disorder Heart failure (NYHA III or IV) Severe liver disease Active hepatitis B or C or HIV infection Active bacterial, fungal or viral disease Malignancy or malignancy in the last 5 years before screening Preexisting immunosuppression Vaccination with a live vaccine in the last 3 months before screening S/p splenectomy Substance abuse Pregnancy or lactation Women: Child/pregnancy with the intended donor Allergy against the investigational drug or part of it Other diseases that prohibit participation in the study (in the opinion of the investigator) Participation in an other interventional study

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Patients receive MIC cell therapy together with standard immunosuppressive therapy | Biological: Mitomycin C-induced peripheral blood mononuclear cells (MICs)<br>* MICs are given intravenously 2 or 7 days before kidney transplantation from a living donor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure is the frequency of adverse events after intravenous administration of MICs within 30 days after transplantation. |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of infection |  | 30 days | 
| Cumulative incidence of CMV reactivation |  | 30 days | 
| Number of patients with PTLD |  | 30 days | 
| Number of patients with delayed graft function |  | 7 days | 
| Number of patients with a pos. CDC and/or ELISA crossmatch |  | day -1 before transplantation | 
| Number of patients with DSA |  | day -1 before transplantation and day 7 and 30 after transplantation | 
| Incidence of biopsy-proven cellular rejection |  | 30 days | 
| Incidence of biopsy-proven antibody-mediated rejection |  | 30 days | 
| Number of patients with stable graft function (S-creatinine < 2mg/dL) |  | 30 days | 
| Patient and graft survival |  | 30 days |