Infusion of donor-derived regulatory dendritic cells in kidney transplant recipients
Allogeneic Regulatory Dendritic Cell (DCreg) Therapy in Live-Donor Renal Transplant Recipients
This study is testing if a special type of immune cell from kidney donors can help first-time kidney transplant recipients stay healthy after their surgery.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 28 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | National Institute of Allergy and Infectious Diseases (NIAID) NIH |
| Drugs / interventions | prednisone |
| Locations | 1 site (Pittsburgh, Pennsylvania) |
| Trial ID | NCT03726307 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and feasibility of a single infusion of donor-derived regulatory dendritic cells (DCreg) in first-time living donor renal transplant recipients. The study involves 14 recipients and their respective living donors, with DCreg prepared from monocytes obtained through leukapheresis. Participants will receive standard immunosuppressive therapy, with adjustments made for the timing and dosage of mycophenolic acid. Follow-up will occur for one week post-leukapheresis for donors and two years for recipients after DCreg infusion.
Who should consider this trial
Good fit: Ideal candidates include first-time living donor kidney transplant recipients and their respective donors who meet the eligibility criteria.
Not a fit: Patients who are not first-time kidney transplant recipients or those who do not meet the donor eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could improve transplant outcomes and reduce the risk of rejection in kidney transplant recipients.
How similar studies have performed: While the approach of using regulatory dendritic cells is innovative, similar studies have shown promise in enhancing transplant outcomes, indicating potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
Donor Eligibility Criteria:
* Able to understand and provide informed consent;
* Meets all standard institutional criteria for kidney donation and Health Agency compliance with kidney donation regulations;
* For females of childbearing potential, a negative urine or serum pregnancy test;
* Negative for tuberculosis by either a negative:
* Purified Protein Derivative (PPD) test or
* Result using an approved interferon-gamma release assay (IGRA) blood test, such as QuantiFERON®-Gold TB or T-SPOT.TB assay,
* Unless the participant has completed treatment for latent tuberculosis, and has a negative chest x-ray.
* Note:
1. PPD or IGRA testing documented to have been performed within 52 weeks before transplant is acceptable
2. Prior recipients of a Bacille Calmette-Guérin (BCG) vaccination must follow the same requirements
* 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 risk factors related to Zika Virus and 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 undergoing first living donor renal transplant;
* For females of childbearing potential, a negative urine or serum pregnancy test upon study entry and agreement to use effective contraception according to Health Agency oversight standards throughout the interval of study participation;
* Cytomegalovirus (CMV) seropositive or, if CMV seronegative must be receiving a kidney from a CMV seronegative donor;
* Negative for tuberculosis by either negative:
* Purified Protein Derivative (PPD) test or
* Result using an approved interferon-gamma release assay (IGRA) blood test, such as QuantiFERON®-Gold TB or T-SPOT.TB assay.
* Exception: If the participant has completed treatment for latent tuberculosis, and has a negative chest x-ray.
* Note:
1. PPD or IGRA testing documented to have been performed within 52 weeks before transplant is acceptable.
2. Prior recipients of a Bacille Calmette-Guérin (BCG) vaccination must follow the same requirements as referenced above.
* And meets all standard institutional criteria for kidney transplant.
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;
* Epstein-Barr Virus (EBV) Immunoglobulin G (IgG) seronegative status;
* 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 other than non-melanomatous skin cancer;
* 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.
* Significant coronary artery disease, Ejection Fraction \<30% or prior acute myocardial infarction;
* 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;
* Women receiving a kidney from a man who has fathered her child(ren), whether or not carried to term; or
* Women receiving a kidney from her biological child.
Where this trial is running
Pittsburgh, Pennsylvania
- University of Pittsburgh, Starzl Transplantation Institute — Pittsburgh, Pennsylvania, United States (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.