Autologous Chimeric Antigen Receptor Engineered T Cell Immunotherapy for Desensitization in Patients Awaiting Kidney Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
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.
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.
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Male or female patients aged 18-65 years with kidney failure requiring hemodialysis. 2. United Network for Organ Sharing (UNOS) listed for kidney transplant for at least 1 year. 3. Patients must meet one of the following two criteria: 1. Protocol-specific cPRA ≥99.5-99.895% AND no matched living donor, ineligible for kidney paired donation programs, have blood group Type O or B, have documentation of virtual crossmatch (current or past) and predictive of a positive physical crossmatch to a deceased donor 2. Protocol-specific cPRA ≥99.9% Protocol-specific cPRA mus…
Interventions
- DrugCyclophosphamide
* 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
- BiologicalCART-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
- BiologicalhuCART19
* 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
- DrugFludarabine
• Cohort 3: 24mg/m\^2 daily x 3
Locations (3)
- Massachusetts General Hospital: Transplantation (Site #: 71107)Boston, Massachusetts
- NYU Langone Health (Site #: 71177)New York, New York
- University of Pennsylvania Medical Center (Site #: 71111)Philadelphia, Pennsylvania