Autologous, unselected CD3+ lymphocytes collected from apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ).
Anti-CD19/4-1BB/CD3ζ CAR T-cell: autologous, unselected CD3+ lymphocytes collected from whole blood or apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ). All patients will receive lymphodepleting, conditioning chemotherapy in the form of cyclophosphamide (500 mg/m2/day) and fludarabine (30 mg/m\^2/day) on Days -5, -4, and -3 prior to a CAR T-cell intravenous, single dose administration on Day 0. Phase 1b: Dose Finding/Escalation Dose Level 1: 0.5 x 10\^6/kg Dose Level 2: 1.0 x 10\^6/kg Dose Level 3: 2.0 x 10\^6/kg Phase 2: Expansion Patients will receive lymphodepleting chemotherapy as indicated prior to receiving the CAR T-cell intravenous, single dose administration on Day 0 at the RP2D as identified during Phase 1b.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Anti-CD19/4-1BB/CD3ζ CAR T-cell: autologous, unselected CD3+ lymphocytes collected from whole blood or apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ). All patients will receive lymphodepleting, conditioning chemotherapy in the form of cyclophosphamide (500 mg/m2/day) and fludarabine (30 mg/m2/day) on Days -5, -4, and -3 prior to a CAR T-cell intravenous, single dose administration on Day 0.
Foothills Medical Centre
Calgary, Alberta, Canada
NOT_YET_RECRUITINGTom Baker Cancer Centre
Calgary, Alberta, Canada
NOT_YET_RECRUITINGAlberta Children's Hospital
Calgary, Alberta, Canada
NOT_YET_RECRUITINGCross Cancer Institute
Edmonton, Alberta, Canada
RECRUITINGStollery Children's Hospital
Edmonton, Alberta, Canada
NOT_YET_RECRUITINGUniversity of Alberta Hospital
Edmonton, Alberta, Canada
RECRUITINGNumber and type of treatment-related adverse events.
Time frame: 3 years
Number of dose limiting toxicities of anti-CD19 CAR T-cells
Time frame: 3 years
Maximum concentration (Cmax).
Time frame: 3 years
Time to maximum concentration (Tmax).
Time frame: 3 years
Area-Under-the-Concentration-vs-time curve (AUC) in peripheral blood and/or bone marrow.
Time frame: 3 years
Overall objective response rate (ORR: proportion of patients with confirmed responses of complete [CR] or partial [PR])
Time frame: 3 years
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