An Exploratory Study on Targeted CD22/CD19 Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy for Enhanced Consolidation Therapy After Initial Remission in High-risk B-cell Acute Lymphoblastic Leukemia
This single-center, open-label, single-arm, prospective study will evaluate the safety, tolerability, and efficacy of CD22/CD19 dual-target CAR-T cell therapy as consolidation treatment in patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) who have achieved first remission after standard induction therapy and consolidation chemotherapy. Approximately 30 patients will be enrolled. Participants will undergo screening, cell collection for CAR-T manufacturing, lymphodepleting chemotherapy, and subsequent CAR-T cell infusion, followed by scheduled safety and efficacy follow-up. Safety assessments will include monitoring for cytokine release syndrome, neurotoxicity, hematologic toxicity, organ toxicity, infections, and other adverse events. Efficacy assessments will include event-free survival, overall survival, progression-free survival, duration of response, relapse, and mortality. Exploratory analyses will assess CAR-T cell kinetic characteristics and clonal evolution after treatment.
• 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).
• Patients who are eligible for enhanced consolidation therapy. Patients with high-risk disease defined as:
• High-risk group based on cytogenetic and molecular features, regardless of MRD status after consolidation; or Standard-risk group with persistent MRD positivity after two cycles of consolidation therapy, indicating a high risk of relapse.
• In addition, patients are unwilling or ineligible to allogeneic hematopoietic stem cell transplantation, and are planned to receive CAR-T cell therapy as consolidation 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.
⁃ 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.