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.
The patient or their legally authorized guardian has signed the informed consent form (ICF), indicating understanding of the purpose and procedures of this clinical trial and willingness to participate.
Age between 18 and 75 years, male or female.
Diagnosis of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) according to the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2024 edition).
Leukemic cells confirmed to express CD19 and/or CD22 by flow cytometry.
Active graft-versus-host disease (GVHD) or autoimmune disease requiring long-term immunosuppressive therapy.
Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent >20 mg/day) within 7 days prior to screening. Physiologic replacement, topical, and inhaled steroids are permitted.
Hypertension not controllable with medication.
Severe cardiac disease, including but not limited to: unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA class ≥III), or severe arrhythmia.
Single group
Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells
Biological/VaccineGenetically 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.
Fludarabine
Drug30 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.
Cyclophosphamide
Drug300 mg/m² intravenous infusion over 30 minutes once daily for 3 consecutive days as lymphodepleting preconditioning prior to CAR-T cell infusion.
Incidence 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.
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.
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.
Complete Remission (CR) Rate
CR rate is the proportion achieving CR. Efficacy assessed by bone marrow examination per international acute leukemia response criteria.
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.
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