An Exploratory Study on Targeted CD22/CD19 Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy for Enhanced Consolidation Therapy of Standard-risk B-cell Acute Lymphoblastic Leukemia
This is a single-center, open-label, single-arm prospective study designed to evaluate the safety, tolerability, and efficacy of dual-target CD22/CD19 chimeric antigen receptor (CAR)-T cell therapy as consolidation treatment in patients with standard-risk B-cell acute lymphoblastic leukemia (B-ALL) in remission. Eligible patients will undergo leukapheresis for CAR-T cell manufacturing, followed by lymphodepleting chemotherapy and CAR-T cell infusion. Patients will be closely monitored for safety, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, and infections. Efficacy endpoints include event-free survival (EFS), overall survival (OS), progression-free survival (PFS), relapse rate, and mortality. Exploratory analyses will assess CAR-T cell expansion kinetics and clonal evolution. The total follow-up duration is planned to be 2 years.
• Patients who have provided written informed consent and are willing and able to comply with study procedures, including scheduled visits, treatment, laboratory tests, and other study-related assessments.
• Patients with cytologically or histologically confirmed B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) according to WHO 2022 criteria, with CD19-positive and/or CD22-positive disease. Patients must have achieved first morphological complete remission (CR1; bone marrow blasts \<5%) after standard induction chemotherapy. Patients may or may not have achieved deep remission, defined as minimal residual disease (MRD) negativity assessed by flow cytometry and/or molecular methods (e.g., quantitative PCR or next-generation sequencing).
• Adult patients with standard-risk B-cell acute lymphoblastic leukemia , as defined by cytogenetic and molecular risk stratification and without high-risk features, who have achieved complete remission (CR) after treatment, received two cycles of long-course intensive consolidation chemotherapy, maintained sustained bone marrow MRD negativity by multiparameter flow cytometry (MFC) and sustained molecular MRD negativity by real-time quantitative polymerase chain reaction (RT-qPCR) or next-generation sequencing (NGS), are not considered to require allogeneic hematopoietic stem cell transplantation (allo-HSCT) for consolidation, and refuse or are ineligible to receive CD19/CD3 bispecific antibody therapy (e.g., blinatumomab), and are therefore planned to receive CAR-T cell immunotherapy as enhanced consolidation therapy followed by long-term maintenance treatment.
• Age between 18 and 85 years, regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Estimated life expectancy ≥3 months.
• Hemoglobin ≥60 g/L (transfusion allowed).
• Absolute neutrophil count ≥1,000/μL and platelet count ≥45,000/μL.
• Adequate organ function, defined as:
⁃ Total bilirubin ≤1.5 × upper limit of normal (ULN) (except Gilbert's syndrome); ALT and AST ≤2.5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); Left ventricular ejection fraction (LVEF) ≥50%, no clinically significant arrhythmia, and no pericardial effusion; Baseline oxygen saturation \>92% on room air; No clinically significant pleural effusion.
⁃ 10\. Subjects of reproductive potential must agree to use effective contraception from enrollment until at least 6 months after completion of the study. Subjects who are pregnant or suspected to be pregnant must notify the investigator immediately.