This investigator-initiated, prospective, single-arm, phase I dose-escalation trial aims to evaluate the safety and tolerability of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia who have failed prior therapies, with the goal of reducing antigen-escape relapse and overcoming poor autologous T-cell fitness through the use of universally available umbilical cord blood T cells.
Patients with relapsed/refractory B-cell acute lymphoblastic leukemia who meet eligibility criteria will receive fludarabine (30 mg/m²/d) and cyclophosphamide (300 mg/m²/d) for three consecutive days as lymphodepleting conditioning, followed by a single intravenous infusion of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells. Dose assignment follows a "3+3" escalation design across three dose levels (4×10⁶, 8×10⁶, and 12×10⁶ CAR-T/kg, ±20%). Dose-limiting toxicity will be assessed during the first 14 days post-infusion to determine the maximum tolerated dose. After CAR-T infusion, patients will be monitored for safety and efficacy at protocol-specified time points through 3 months, with long-term follow-up continuing up to 15 years post-infusion. A total of 18 patients will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Genetically modified umbilical cord blood-derived T cells expressing chimeric antigen receptors targeting both CD19 and CD22. Administered as a single intravenous infusion on Day 0 following lymphodepleting chemotherapy. Dose levels: 4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg (±20%) according to 3+3 dose escalation design.
30 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.
300 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGIncidence and Severity of Dose-Limiting Toxicity (DLT)
DLT is defined as treatment-related adverse events occurring within 14 days post-infusion. Non-hematologic DLT: Grade ≥3 toxicity not reducible to ≤ Grade 1 within 72 hours. Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) persisting \>21 days, not attributable to underlying disease. Predefined exclusion criteria include tumor lysis syndrome, electrolyte disturbances, hypogammaglobulinemia, transient laboratory abnormalities, febrile neutropenia, and others per protocol. CRS/ICANS graded per ASTCT 2019, aGVHD per modified Glucksberg, other AEs per CTCAE v5.0.
Time frame: Within 14 days after CAR-T cell infusion
Objective Response Rate (ORR)
ORR is the proportion of subjects achieving CR/CRi at 1 and 3 months post-infusion. Efficacy assessed by bone marrow examination per international acute leukemia response criteria.
Time frame: 1 and 3 months post-infusion
Minimal Residual Disease (MRD) Negativity Rate
MRD negativity rate is the proportion of subjects achieving MRD-negative status by flow cytometry at 1 and 3 months post-infusion.
Time frame: 1 and 3 months post-infusion
Complete Remission (CR) Rate
CR rate is the proportion achieving CR. Efficacy assessed by bone marrow examination per international acute leukemia response criteria.
Time frame: 1 and 3 months post-infusion
Progression-Free Survival (PFS)
PFS is defined as time from infusion to disease progression, relapse, or death. Median PFS and 12-/24-month PFS rates will be estimated by Kaplan-Meier method.
Time frame: From infusion up to 24 months
Overall Survival (OS)
OS is defined as time from infusion to death from any cause. Median OS and 12-/24-month OS rates will be estimated by Kaplan-Meier method.
Time frame: From infusion up to 24 months
CAR-T Cell Expansion and Persistence
CAR-T cell levels and vector copy number (VCN) in peripheral blood will be measured.
Time frame: Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
PK parameters: Cmax(Peak Plasma Concentration)
Time frame: Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
PK parameters: Tmax
Time frame: Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
PK parameters: AUC₀-₂₈d, AUC₀-₉₀d.
Time frame: Up to 90 days post-infusion
CAR-T Cell Expansion and Persistence
Proportion of subjects with detectable CAR-T cells at 3 and 6 months, and duration of persistence will be recorded.
Time frame: At 3 and 6 months
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