Allogeneic Regulatory Dendritic Cell (DCreg) Renal Study

NCT ID: NCT03726307

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-10
• Study Completion Date: 2027-03-31

Brief 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.

Detailed Description

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Note: Participants will not be withdrawn from known effective therapy for the purpose of participating in this research.

Conditions

Kidney Transplant; Renal Transplant Recipients

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DCreg: 0.5 million cells/kg+SOC

N=3 participants will receive 0.5 (± 0.1) million cells/kg body weight as a single infusion.

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.

Group Type: EXPERIMENTAL

DCreg: 0.5 million cells/kg+SOC

Intervention Type: BIOLOGICAL

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 million cells/kg+SOC

N=3 participants will receive 1.2 (± 0.2) million cells/kg body weight as a single infusion.

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.

Group Type: EXPERIMENTAL

DCreg: 1.2 million cells/kg+SOC

Intervention Type: BIOLOGICAL

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/kg+SOC

N=8 participants will receive 25 to 5.0 million cells /kg body weight as a single infusion.

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.

Group Type: EXPERIMENTAL

DCreg:2.5 to 5.0 million cells/kg+SOC

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Regulatory Donor-Derived Dendritic Cells (DCreg); Regulatory Donor-Derived Dendritic Cells (DCreg); Regulatory Donor-Derived Dendritic Cells (DCreg)

Eligibility Criteria

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.

• 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).

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Angus W. Thomson PhD DSc

OTHER

Sponsor Role: lead

Responsible Party

Angus W. Thomson PhD DSc

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amit D. Tevar, MD, FACS

Role: STUDY_CHAIR

University of Pittsburgh: Starzl Transplantation Institute

Locations

University of Pittsburgh, Starzl Transplantation Institute

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.

Reference Type: BACKGROUND

PMID: 24472190 (View on PubMed)

Haas M. The Revised (2013) Banff Classification for Antibody-Mediated Rejection of Renal Allografts: Update, Difficulties, and Future Considerations. Am J Transplant. 2016 May;16(5):1352-7. doi: 10.1111/ajt.13661. Epub 2016 Feb 4.

Reference Type: BACKGROUND

PMID: 26696524 (View on PubMed)

Related Links

https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

NIH NCI Common Terminology Criteria for Adverse Events (CTCAE)

Other Identifiers

U01AI136779

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19040393

Identifier Type: -

Identifier Source: org_study_id