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ACTIVE NOT RECRUITING

NCT03726307

PHASE1

Allogeneic Regulatory Dendritic Cell (DCreg) Renal Study

Sponsor: Angus W. Thomson PhD DSc

View on ClinicalTrials.gov

Summary

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.

Official title: Allogeneic Regulatory Dendritic Cell (DCreg) Therapy in Live-Donor Renal Transplant Recipients

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2019-04-10

Completion Date

2027-03

Last Updated

2025-06-15

Healthy Volunteers

Yes

Conditions

Kidney Transplant Renal Transplant Recipients

Interventions

BIOLOGICAL

DCreg: 0.5 million cells/kg+SOC

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.

BIOLOGICAL

DCreg: 1.2 million cells/kg+SOC

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.

BIOLOGICAL

DCreg:2.5 to 5.0 million cells/kg+SOC

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.

Inclusion Criteria: Donor Eligibility Criteria: * Able to understand and provide informed consent; * Male or female \>/= 18 years of age * Meets all standard institutional criteria for kidney donation and Health Agency criteria for kidney donation; * For females of childbearing potential, a negative urine or serum pregnancy test; * Negative for Human Immunodeficiency Virus type 1 (HIV) -1 (antigen and Nucleic Acid Testing (NAT)), HIV-2, Human T-cell leukemia virus type 1 (HTLV-1), and HTLV-2; * Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and core antibody), and Treponema pallidum infection; * Negative for West Nile Virus; * Negative health history for Creutzfeldt-Jakob disease; * No live vaccines within 8 weeks prior to leukapheresis; * No medical condition(s) that the investigator deems incompatible with participation in the trial; and * No use of investigational drugs within 12 weeks of participation. Recipient Inclusion Criteria: * Must be able to understand and provide informed consent; * Is \>/= 18 years old at the time of informed consent; * Is undergoing a living donor renal transplant; * For females of childbearing potential, a negative urine or serum pregnancy test upon study entry * The candidate agrees to use contraception with a method that is more than 80% effective (see FDA Office of Women's Health (http://www.fda.gov/birthcontrol). Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) to be used from one month before study treatment begins until one month after study completion; * Cytomegalovirus (CMV) seropositive or, if CMV seronegative must be receiving a kidney from a CMV seronegative donor; * Has a negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved IGRA blood test, such as QuantiFERON®-Gold TB or T-SPOT-TB assay OR has completed treatment for latent tuberculosis and has a negative chest x-ray. PPD or IGRA testing must occur within 52 weeks before transplant. These requirements apply as well to prior recipients of Bacille Calmette-Guérin (BCG) vaccination; * Meets all standard institutional and Health Agency criteria for kidney transplant. * Vaccines up to date as per DAIT guidance for patients in transplant trials (Refer to Manual of Operations). Study Exclusion Criteria: * Panel Reactive Antibody (PRA \>20%); * Positive T or B Cell Flow Crossmatch prior to transplant; * Presence of donor specific antibody (DSA) ≥ to mean fluorescence intensity (MFI) of 1000, or DSA between 500 and 1000, if a specific shared epitope pattern is present; * Recipient of multi-organ transplant; * Any prior renal or extra-renal transplant with HLA class II antigen mismatch shared with prior organ; * Epstein-Barr Virus (EBV) Immunoglobulin G (IgG) negative if the donor is EBV positive; * Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (HCV) antibody (if hepatitis C antibody positive, confirm negative infection by HCV RNA), or positivity for hepatitis B surface antigen; * History of malignancy witin the past 5 years unless standard institutional criteria detailed in Appendix 6 have been met; * High risk for recurrence of renal disease: Hemolytic Uremic Syndrome Thrombotic Thrombocytopenic Purpura (HUS-TTP); Focal Segmental Glomerular Sclerosis (FSGS); or Aggressive native kidney disease. * Compensated and decompensated cirrhosis of liver and/or portal hypertension; * Chronic Obstructive Pulmonary Disease requiring nasal oxygen, and/or pulmonary hypertension (mean pulmonary pressure \>45mm/hg); * Any history of stroke with neurological deficit; * Any condition that, in the opinion of the investigator, confers excessive risk for participation in this phase 1 study; * Presence of a condition that requires treatment with an immunosuppressive agent, other than a physiologic dose of corticosteroid; * Live vaccines within 8 weeks prior to transplant; * Use of investigational drugs within 12 weeks of participation; * Woman receiving a kidney from a man who has fathered her child(ren), whether or not carried to term; or * Woman receiving a kidney from her biological child.

Locations (1)

University of Pittsburgh, Starzl Transplantation Institute

Pittsburgh, Pennsylvania, United States