Dual-Targeted Umbilical Cord Blood CAR-T Cells Against CD19 and CD22 for the Treatment of Relapsed or Refractory Acute B-Cell Lymphoblastic Leukemia

Prior treatment

• 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.
• 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.
• Malignancy other than B-ALL within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after radical surgery.
• Planned surgery within 2 weeks after study treatment (subjects scheduled for local anesthesia surgery may participate).
• Receipt of other interventional investigational drugs within 1 month prior to ICF signing.

Other illness

• Active graft-versus-host disease (GVHD) or autoimmune disease requiring long-term immunosuppressive therapy.
• Hypertension not controllable with medication.
• Unstable systemic disease as judged by the investigator, including but not limited to: severe hepatic, renal, or metabolic disease requiring medication.
• History of solid organ transplantation.
• Uncontrolled active infection.
• Positive for HBsAg, or positive for HBcAb with detectable HBV DNA in peripheral blood; positive for HCV antibody with detectable HCV RNA; positive for HIV antibody; positive for CMV DNA; positive for syphilis serology.
• Psychiatric illness, consciousness disorder, or central nervous system disease.
• Other conditions deemed unsuitable for enrollment by the investigator.

Other

• Pregnant or breastfeeding women.

• 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.
• ECOG performance status 0-2.
• Life expectancy ≥12 weeks.
• Adequate organ function at screening, meeting all of the following laboratory criteria:
  • Hematology: absolute neutrophil count (ANC) ≥1×10⁹/L; absolute lymphocyte count (ALC) ≥0.3×10⁹/L; platelet count ≥20×10⁹/L; hemoglobin ≥60 g/L.
  • Hepatic function: ALT and AST ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5× ULN.
  • Renal function: creatinine clearance (CrCl) ≥40 mL/min (by Cockcroft-Gault formula).
  • Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
  • Oxygen saturation \>91%.
  • Left ventricular ejection fraction (LVEF) ≥50%.
• The subject and their spouse agree to use effective contraceptive measures (excluding rhythm method) from ICF signing through 1 year after CAR-T cell infusion.