ECP-DL Cell Infusion for Induction in Living Donor Kidney (LDK) Transplants

Northwestern University

Status and phase: Not yet enrolling; Phase 1

Conditions: Kidney Transplant Failure and Rejection; Kidney Transplant; Complications

Treatments: Device: ECP-DL treated mononuclear cell infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT07083830

STU00222957

Details and patient eligibility

About

This is a phase 1 trial, 36 month duration for subjects with end-stage renal disease (ESRD). The objectives of the trail are1) Determine the safety of ECP-DL cell infusion in living donor renal transplant recipients. 2) Determine rates of graft rejection and compare to historical controls.

One week prior to planned LDK transplant the donor and recipient pair will be seen for ECP-DL preparation and infusion. Donors will undergo one single unstimulated peripheral blood mononuclear cell collection using the THERAKOS® CELLEX® Photopheresis System; the cell product will then undergo ECP treatment to make ECP-DL, which will then be infused into the recipient. One week later, recipients (n=12) will undergo LDK transplant using standard of care maintenance immunosuppression without antibody induction therapy. Subsequent patients will receive cell infusions in escalating cell doses. A minimum of two months will be used as an interval between ECP-DL treatment in each tier. A staggered approach for moving to the next tier will be employed waiting no less than two months to ensure absence of adverse events using the following tier dosing schema:

Tier 1: 0.5 x 10^9 ECP-DL treated cells (n=4) Tier 2: 1 x 10^9 ECP-DL treated cells (n=4) Tier 3: 2 x 10^9 ECP-DL treated cells (n=4)

Following transplant, LDK recipients will undergo ECP using the Therakos system on two consecutive days per month for 6 months (12 treatments). Peripheral IV access will be used whenever possible.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Recipient age ≥30 and less than 70 years old.
• Donor age ≥18 and ≤ 70 years old.
• Recipient of a first kidney transplant from a living unrelated or living related donor that is not HLA-identical to the donor.
• Donor willing to undergo cell collection for ECP-DL cell preparation and infusion.
• Donors will be screened and tested for HIV-1 (antigen and nucleic acid), HIV-2, hepatitis B virus (HBV, nucleic acid and surface and core antigen), hepatitis C virus (HCV, antigen and nucleic acid), Treponema pallidum (syphilis), West Nile Virus (WNV), and CJD (screening only). and tested for human T-lymphotropic virus types 1 and 2 (HTLV-1, HTLV-2) and CMV, in accordance with established UNOS guidelines for solid organ donors.
• Donors and recipients who test negative for TB using QuantiFERON gold assay.
• Must be willing and able to comply with protocol-required visit schedule and visit requirement.
• Patients who are single-organ recipients (kidney only).
• Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period. Both male and female transplant recipients must agree to the use of highly effective birth control for 12 months following ECP-DL procedure. Individuals unwilling to do so will be excluded from study participation.
• Subjects are able to understand the consent form and give written informed consent.

Exclusion criteria

RECIPIENT

• Known sensitivity or contraindication to everolimus, tacrolimus, or psoralen.
• Aphakia.
• Has undergone splenectomy
• Patients with light-sensitive diseases including (but not limited to) systemic lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porhyria, xeroderma pigmentosum, and albinism
• Patient with significant or active infection.
• Patients with a positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
• Patients with PRA >80%
• Patients with current or historic donor specific antibodies
• Body Mass Index (BMI) of < 18 or > 40
• Patients who are pregnant or nursing mothers
• Patients whose life expectancy is severely limited by diseases other than renal disease
• Ongoing active substance abuse, drug or alcohol
• Major ongoing psychiatric illness or recent history of noncompliance
• Significant cardiovascular disease
• Malignancy within 3 years, excluding nonmelanoma skin cancers
• Subjects with cerebrovascular vascular disease with recent (< 6 months) stroke
• Serologic evidence of infection with HIV or HBVs Ag positive
• Recipient is EBV serologic negative
• Donor CMV serologic positive to recipient CMV serologic negative
• Recipient tests positive for HCV viral load by PCR
• Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet count < 100,000/mm3; triglyceride > 400 mg/dl; total cholesterol > 300 mg/dl
• Investigational drug within 30 days prior to transplant surgery
• Anti-T cell therapy within 30 days prior to transplant surgery
• Documented severe liver disease, defined as bridging fibrosis or cirrhosis on liver biopsy
• Poorly controlled diabetes, defined as HbA1c of > 8.0
• PT/INR > 2.0
• SBP < 90 or > 180mm Hg, HR > 120 or <50bpm, Temp > 99.5F on day of proposed ECP-DL procedure
• Patients receiving concomitant enteral or topical medical therapy with potentially photosensitizing effects

DONOR

• Lack of possible peripheral IV access (two access sites)
• Has undergone splenectomy
• Donor tests positive for HCV viral load by PCR
• PT/INR > 2.0; or known hyper or hypo coagulable disorders
• Hgb < 10.0
• platelet count < 100,000
• SBP < 90 or > 160mm Hg, HR > 120 or <50bpm, Temp > 99.5F on day of proposed ECP-DL procedure
• Donors who cannot tolerate extracorporeal volume during PBMC collection

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 1 patient group

ECP-DL Cell Therapy Arm

Experimental group

Description:

Participants will receive escalating doses of ECP-DL (extracorporeal photopheresis-derived dendritic-like) cells starting on Day -7 prior to living donor kidney transplantation. The intervention aims to evaluate the safety and immunomodulatory effects of ECP-DL cell infusion in the context of renal transplantation.

Treatment:

Device: ECP-DL treated mononuclear cell infusion