This study will evaluate the safety and feasibility of treatment involving a single infusion of donor-derived regulatory dendritic cells (DCreg) in first time, living donor renal transplant recipients. DCreg will be prepared from monocytes obtained by leukapheresis from prospective (non-mobilized) living kidney donors and infused into the respective recipients 7 days before renal transplantation. This study will enroll 28 subjects (14 recipients, 14 donors). The duration of follow-up will be: * 1 week following the leukapheresis procedure for donors and * 2 years following their DCreg infusion for kidney recipients.
This clinical trial is a single-center, open-label, dose-escalation, phase 1 study, enrolling N=14 de novo kidney transplant recipients and their respective living donors. The study objective is to evaluate the safety and feasibility of a single infusion of donor-derived regulatory dendritic cell (DCreg) treatment. Transplant recipients will receive combination immunosuppressive agents according to the site's Standard of Care (SOC) regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose, due to increased drug bioavailability in recipients with low kidney function defined by glomerular filtration rate (GFR). Consequently, participants will be maintained on triple immunosuppressive therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide. Note: Participants will not be withdrawn from known effective therapy for the purpose of participating in this research.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
DCreg 0.5 (±0.1) million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.
DCreg 1.2 (±02) million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.
DCreg 2.5 to 5.0 million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.
University of Pittsburgh, Starzl Transplantation Institute
Pittsburgh, Pennsylvania, United States
Composite Outcome: Proportion of Participants who Experience any of the Pre-Specified Safety Events
Safety will be assessed by summarizing the proportion of participants who experience any of the following events from the initiation of the regulatory dendritic cells (DCreg) infusion administered 7 days prior to kidney transplant to 1 year post-transplant: * Recipient death attributed to receipt of DCreg, * NCI-CTCAE Grade 4 or higher DCreg infusion reaction, * NCI-CTCAE Grade 4 or higher infection, * Malignancy other than non-melanoma skin cancer, * Pre-transplant Donor Specific Antibodies (DSA), * Post-transplant DSA, * Biopsy-proven acute rejection (BPAR) by BANFF 2017 criteria (grade ≥2A), or * Non-surgical graft loss. * Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
Time frame: Seven Days Prior to Transplant Surgery(e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant
Incidence of Death Attributed to Participant Receipt of Regulatory Dendritic Cells (DCreg)
The occurrence of death among participants who receive DCreg treatment.
Time frame: Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant
Incidence of Adverse Event: CTCAE Grade 4 or Higher Infusion Reaction
The number of Grade 4 or higher infusion reaction(s) among participants who receive regulatory dendritic cells (DCreg) infusion, graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
Time frame: Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant
Incidence of Adverse Event:CTCAE Grade 4 or Higher Infection
The number of Grade 4 or higher infection(s) among participants who receive regulatory dendritic cells (DCreg) infusion, graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
Time frame: Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant
Incidence of Adverse Event: Malignancy
The number of malignancies among participants who receive regulatory dendritic cells (DCreg) infusion. Not included in this incidence outcome: non-melanoma skin cancer(s).
Time frame: Seven Days Prior to Transplant Surgery(e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant
Incidence of Pre-Transplant Donor Specific Antibodies (DSA)
The number of pre-transplant DSA among participants occurring after DCreg infusion and before transplant.
Time frame: Baseline (Seven Days Prior to Transplant Surgery, "Pre" -Regulatory Dendritic Cells (DCreg)) Infusion) up to within 48 Hours of Transplant
Incidence of Post-Transplant Donor Specific Antibodies (DSA)
A de novo DSA occurring within the first year post-transplant.
Time frame: Day 0 (Transplant Surgery) up to 1-Year Post-Transplant
Incidence of Biopsy-Proven Acute Rejection
Acute kidney allograft rejection is defined by a kidney (renal) allograft biopsy classification of grade 2A or higher. Classification method: Banff 2013. The Banff 2013 classification for antibody-mediated rejection is a recognized standard in renal allograft pathology.
Time frame: Day 0 (Transplant Surgery) up to 1-Year Post-Transplant
Incidence of Non-Surgical Graft Loss
Graft loss not associated with the transplant surgery.
Time frame: Day 0 (Transplant Surgery) up to 1-Year Post-Transplant
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