CAR-T Cell Therapy for Desensitization in Kidney Transplantation
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male or female patients aged 18-65 years with kidney failure requiring hemodialysis.
Protocol-specific cPRA ≥99.5%
No suitable living donor OR has been active in a kidney paired donation program but not received a match within 12 months
Have blood group Type O or B, and predictive of a positive virtual crossmatch to an available deceased donor.
Disqualifiers
Subjects with indwelling catheters as primary access for hemodialysis
Previous solid organ (except kidney) or bone marrow transplant
BMI ≥35 kg/m²
Subjects who have preserved or oliguric urine output > 100 cc/day with history of recurrent UTI (2 in 6 months or 3 in 1 year, see study definitions)
Trial design
Design model
Sequential
Treatments tested in this trial
Cyclophosphamide
Drug* 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
CART-BCMA
Biological/Vaccine* 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
huCART19
Biological/Vaccine* 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
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Participant CohortsExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
The timing of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)
Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL (≥600/microL for those with Duffy null associated phenotype) and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity
Time frame
12 months after infusion of CART-BCMA with huCART-192
The frequency of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)
Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by ASTCT consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL (≥600/microL for those with Duffy null associated phenotype) and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity
Time frame
12 months after infusion of CART-BCMA with huCART-193
The severity of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)
Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by ASTCT consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL (≥600/microL for those with Duffy null associated phenotype) and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity
Time frame
12 months after infusion of CART-BCMA with huCART-194
The proportion of apheresed subjects who receive the intended/planned Chimeric antigen receptor T (CAR T) cell dose in the respective cohort
Time frame
From time of lymphodepletion to 12 monthsSecondary outcomes
1
The proportion of subjects meeting the predefined Calculated Panel Reactive Antibody (cPRA) reduction criteria after the infusion of CART-BCMA + huCART-19
Time frame
26 weeks after the infusion2
Duration of Calculated Panel Reactive Antibody (cPRA) response
Time frame
From time of infusion to 12 months3
For subjects who are transplanted, the proportion of subjects experiencing acute cellular rejection or antibody mediated rejection, delayed graft function (as well as AKI), graft loss OR De Novo donor specific antibody
Time frame
3 years after transplantation4
The proportion of subjects with opportunistic infections
Time frame
From time of infusion to 12 months or 3 years after transplantationSponsors and contacts
Click on the lead sponsor to view all of their trials.
National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
University of Pennsylvania Clinical Cell and Vaccine Production Facility (CVPF)
Collaborator
Source ClinicalTrials.gov