CD19 Sequential CD22 In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Voluntarily agrees to participate in the study, has signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
• Diagnosis of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) according to the World Health Organization (WHO) classification, confirmed by bone marrow aspirate morphology, flow cytometry, or histopathology, with tumor cells shown by immunophenotyping or flow cytometry to express CD19 and CD22. Relapsed/refractory B-ALL is defined as meeting at least one of the following four criteria:

Relapse within 6 months after first remission; Primary refractory disease: failure to achieve complete remission after 2 cycles of standard chemotherapy; Failure to achieve complete remission or relapse after one or more lines of salvage chemotherapy; Relapse after hematopoietic stem cell transplantation.

• Male or female participants aged 14 to 75 years, inclusive.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Estimated life expectancy of more than 3 months from the date of signing the informed consent form.
• Adequate renal, hepatic, cardiac, and pulmonary function, defined as follows:

Creatinine clearance (estimated by the Cockcroft-Gault formula) ≥60 mL/min or serum creatinine ≤1.5 × the upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN), total bilirubin≤1.5×ULN; Cardiac ejection fraction≥50%, no pericardial effusion on echocardiography, and no significant abnormalities on electrocardiogram (ECG); No clinically significant pleural effusion, and oxygen saturation >92% on room air at baseline.

• Participants of reproductive potential must agree to use highly effective contraception before enrollment and for at least 12 months after SL1CC infusion. A negative serum pregnancy test is required for women of childbearing potential at screening. Participants must immediately notify the investigator if pregnancy occurs or is suspected.

Exclusion Criteria:

• The patient has severe cardiac dysfunction, or left ventricular ejection fraction (LVEF) <50%, or a history within the 12 months prior to enrollment of myocardial infarction, coronary angioplasty or coronary stent implantation, unstable angina, clinically significant arrhythmia, or other severe cardiovascular diseases.
• A history of severe pulmonary disease associated with impaired lung function.
• Concurrent progressive malignancy other than acute lymphoblastic leukemia.
• Severe active infection that cannot be effectively controlled, defined as sepsis or an infection with an uncontrolled infectious focus. Participants may be enrolled after the infection has been adequately controlled.
• Severe autoimmune disease or congenital immunodeficiency.
• Active hepatitis B or hepatitis C infection, defined as hepatitis B virus DNA (HBV DNA) or hepatitis C virus RNA (HCV RNA) levels above the lower limit of detection.
• Human immunodeficiency virus (HIV) infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection; has received a live vaccine within 4 weeks, or is anticipated to require a live vaccine during the study period.
• History of severe immediate hypersensitivity reactions to any drug required in this study, including antibiotics, or to biological products.
• Prior treatment with any gene therapy product or any in vivo CAR-T therapy, or known pre-existing neutralizing immunity to the lentiviral vector.
• Active central nervous system (CNS) leukemia or leptomeningeal involvement not controlled after adequate intrathecal therapy; cerebrospinal fluid examination is required during screening.
• The patient has severe autoimmune disease, congenital immunodeficiency or active autoimmune disease requiring ongoing systemic immunosuppressive treatment, or is currently within the washout period after having received medications that may affect CAR-T cell immunotherapy, or is anticipated to require medications during the study period that may affect CAR-T cell immunotherapy treatment, or active GVHD requiring systemic therapy.
• Pregnancy or breastfeeding (lactation).
• The investigator judges that the patient is unlikely to complete all visits and procedures required by the study protocol (including medium- and long-term follow-up visits), such as insufficient willingness of the patient and their family members to participate in the study, refusal to participate, inability of the patient to fully cooperate with the study arrangements, or inadequate compliance on the part of the patient and their family members.
• Any other severe physical or psychiatric disorder or clinically significant laboratory abnormality that may increase the risk associated with study participation, interfere with the interpretation of study results, or, in the investigator's judgment, make the participant unsuitable for participation in the study.