CAR-T Cell Therapy for Desensitization in Kidney Transplantation

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.

Conditions

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

Interventions

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

Sponsors & Collaborators

• University of Pennsylvania Clinical Cell and Vaccine Production Facility (CVPF)

  collaborator UNKNOWN

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Vijay Bhoj, M.D., Ph.D. · University of Pennsylvania Medical Center: Transplantation

• Ali Naji, MD, Ph.D. · University of Pennsylvania Medical Center: Transplantation

• Alfred Garfall, MD · University of Pennsylvania Medical Center: Transplantation

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-05-09

Primary Completion

2028-12-15

Completion

2042-12-15

FDA Drug

Yes

Countries

• United States

Study Locations