Autologous Chimeric Antigen Receptor Engineered T Cell Immunotherapy for Desensitization in Patients Awaiting Kidney Transplantation
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.
• Male or female patients aged 18-65 years with kidney failure requiring hemodialysis.
• United Network for Organ Sharing (UNOS) listed for kidney transplant for at least 1 year.
• Patients must meet one of the following two criteria:
∙ 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
‣ Protocol-specific cPRA ≥99.9% Protocol-specific cPRA must be rounded from three significant figures measured ≤90 days from the time of enrollment (i.e., cPRA of 0.994500 or 0.998500 would be eligible) using the web-based OPTN cPRA calculator (https://optn.transplant.hrsa.gov/resources/allocation-calculators/cpra-calculator/); accounting for HLA-A, -B, -C, -DRB1, -DRB3/4/5, and -DQB1 Luminex Single Antigen Beads (SAB) with MFI ≥3000; 1 archived sample within 6 months of screening required.
• Based on center-specific listing policies, a cPRA in UNet Waitlist that is ≥99.5% (the candidate must be eligible for additional priority of kidneys equivalent to individuals with a 100% cPRA)
• Able to understand and give written informed consent to participate in all aspects of the study.
• Willing to stay within 2 hours of the home study site for at least 28 days after the last T cell infusion
• Subjects of reproductive potential must agree to use contraception for at least one year after CAR T Cell infusion
• In the absence of contraindication, vaccinations must be up to date per the DAIT Guidance for Patients in Transplant Trials and include TdAP
• Positive for EBV capsid IgG
⁃ Negative testing for latent TB infection within 3 months prior to enrollment. Testing should be conducted using either a PPD or interferon-gamma release assay (i.e. QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection must complete appropriate therapy for Latent Tuberculosis Infection (LTBI). A subject is considered eligible only if they have a negative test for LTBI within 3 months prior to enrollment OR they have appropriately completed LTBI therapy prior to transplant. Latent TB infection treatment regimens should be among those endorsed by the CDC
⁃ Hemoglobin ≥9g/dL
⁃ ANC ≥ 1,800/μL, \> 1,200/ μL for patients with Duffy-null associated neutrophil count (DANC)
⁃ Absolute Lymphocyte Counts ≥500/μL or CD3 T cell Count ≥150/μL
⁃ Platelet count ≥120,000/μL