NCT06056102

CAR-T Cell Therapy for Desensitization in Kidney Transplantation

Autologous Chimeric Antigen Receptor Engineered T Cell Immunotherapy for Desensitization in Patients Awaiting Kidney Transplantation

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This research study is for people who have been waiting for a kidney transplant for at least one year, and who have a cPRA of 99.5% or higher. Having a cPRA of 99.5% or higher means that your immune system would reject 99.5% of kidneys available for transplant. The study will test whether new products called Chimeric Antigen Receptor T Cells (CAR T Cells), when given with chemotherapy, is safe and will reduce cPRA. The main study will last up to 2 years: Participants will have up to 30 clinic or hospital visits over a one-year period. If a transplant takes place, there will be 9 more visits after transplant. Long term follow up is required by the Food and Drug Administration (FDA) for 15 years after receiving CAR T cell. The primary objective is to evaluate the safety and feasibility of administering CART BCMA + huCART-19 following lymphodepletion, including determination of optimal tolerated regimen (OTR) and/or recommended phase 2 regimen, according to the incidence of dose limiting toxicity (DLT) in highly sensitized patients awaiting kidney transplant.

Detailed description

CTOT-46 will enroll up to up to 20 highly sensitized kidney transplant candidates at 3 centers. There will be a safety run-in and 3 treatment cohorts to assess the safety and pharmacodynamics of CART-BCMA and huCART-19. Following screening and enrollment, the subject will undergo leukapheresis to collect T cells for CAR T cell manufacturing. Subsequently, subjects will undergo lymphodepleting chemotherapy followed by CART-BCMA and huCART19 cell infusions. A secondary objective is to evaluate the efficacy of study treatment to reduce cPRA and determine the duration cPRA reduction.

Conditions

• Kidney Transplant
• Kidney Failure
• End Stage Renal Failure on Dialysis

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	* Safety Run-in: 375mg/m\^2 daily x 3 * Cohort 1: 375mg/m\^2 daily x 3 * Cohort 2: 375mg/m\^2 daily x 3 * Cohort 3: 375mg/m\^2 daily x 3
BIOLOGICAL	CART-BCMA	* Safety Run-in: 5 x 10\^7 CAR T cells * Cohort 1: 1.5 x 10\^8 CAR T cells * Cohort 2: 1.5 x 10\^8 CAR T cells * Cohort 3: 5 x 10\^8 CAR T cells
BIOLOGICAL	huCART19	* Safety Run-in: 5 x 10\^7 CAR T cells * Cohort 1: 1.5 x 10\^8 CAR T cells * Cohort 2: 1.5 x 10\^8 CAR T cells * Cohort 3: 5 x 10\^8 CAR T cells
DRUG	Fludarabine	• Cohort 3: 24mg/m\^2 daily x 3

Timeline

• Start date: 2024-05-09
• Primary completion: 2028-12-15
• Completion: 2042-12-15
• First posted: 2023-09-28
• Last updated: 2025-11-26

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study