A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LCAR-AIO, a triple-targeted cell preparation targeting CD19/CD20/CD22, in patients with relapsed/refractory B-cell acute lymphocytic leukemia
This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of LCAR-AIO in patients ≥ 18 years of age with relapsed or refractory B-cell acute lymphocytic leukemia. Patients who meet the eligibility criteria will receive a single dose of LCAR-AIO infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
LCAR-AIO Cells before treatment with LCAR-AIO cells, subjects will receive a conditioning regimen (IV infusion of cyclophosphamide 300 mg/m\^2 and fludarabine 30mg/m\^2 once daily (QD) for 3 days.
Beijing Gobroad BoRen Hospital
Beijing, Beijing Municipality, China
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment
Time frame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Recommended Phase 2 dose (RP2D) finding
RP2D established through ATD+BOIN design
Time frame: [Time Frame: 30 days after LCAR-AIO infusion (Day 1)]
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AIO infusion
Time frame: [Time Frame: 2 years after LCAR-AIO infusion (Day 1)]
Overall response rate (ORR)
Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or CRi after treatment via LCAR-AIO cell infusion
Time frame: [Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
Time to Response (TTR)
Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-AIO to the date of the first response evaluation of the subject who has met all criteria for CR or CRi.
Time frame: [Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
Duration of Response (DoR)
Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or CRi) to the first documented relapse evidence of the responders
Time frame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
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Relapse-free survival (RFS)
Relapse-free survival (RFS) is defined as the time from the date of first infusion of the LCAR-AIO to the first documented disease relapse or death (due to any cause), whichever occurs first
Time frame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject
Time frame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Incidence of anti-LCAR-AIO antibody and positive sample titer
Venous blood samples will be collected to measure LCAR-AIO positive cell concentrations and the transgenic level of LCAR-H93T, at the time points when anti-LCAR-AIO antibody serum samples are evaluated
Time frame: [Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)]