CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Patients aged ≥18 and \<70 years, of any gender;
* diagnosed with B-ALL/LBL according to the criteria of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2020.v1) and B-cell Lymphoma Clinical Practice Guidelines (2020.v1);
* meeting either of the following two criteria: (1) Previous targeted CD19 therapy, including bispecific antibodies, ADC drugs, and CAR-T, with continued CD19 expression; (2) Patients with hematological malignancies who have not received CD19-targeted therapy in the past, with weakly positive CD19 expression;
* At the time of screening, the number of blasts in the bone marrow is 25% (bone marrow morphology) and/or extramedullary lesions;
* Meeting the diagnosis of relapsed/refractory B-ALL/LBL, including any of the following situations: a. Primary refractory patients who have not achieved complete remission after two cycles of standardized chemotherapy or patients who have not achieved complete remission after multiple salvage chemotherapy regimens; b. Patients who relapse within 12 months after achieving complete remission or relapse after 12 months of achieving complete remission and have not achieved complete remission after one or more courses of standard treatment induction; c. Patients who relapse after hematopoietic stem cell transplantation or after CAR-T therapy targeting the same target;
* Other relapsed/refractory CD19 weakly expressing hematological malignancies;
* Creatinine clearance rate \> 60 ml/min (Cockcroft and Gault formula); for patients without liver involvement, total serum bilirubin \< 3 times the upper limit of normal, and both serum ALT and AST \< 5 times the upper limit of the normal range.
* Echocardiography shows left ventricular ejection fraction (LVEF) of 250%;
* Finger pulse oxygen saturation \> 92%;--Estimated survival period of more than 3 months;
* Estimated survival period of more than 3 months;
* ECOG score of 0-2;
* The subject or his/her legal guardian voluntarily participates in this trial and signs the informed consent form.

Exclusion Criteria:

* Acute promyelocytic leukemia (APL);
* presence of hereditary syndromes such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known myelodysplastic syndrome;
* uncontrolled active central nervous system leukemia (CNSL), i.e., cerebrospinal fluid (CSF) classification CNS 3;
* prior administration of antineoplastic therapy before infusion; exclusion criteria include: a. Received systemic chemotherapy within 1 week (excluding pre-treatment); b. Those who have received monoclonal antibody treatment, with the time from the last monoclonal antibody infusion to the screening being less than 5 half-lives or 4 weeks (whichever is shorter); c. Received donor lymphocyte infusion (DLI) within 6 weeks;
* Had uncontrolled severe active infection at screening;
* Had a history of severe heart disease, including: severe heart dysfunction (according to the New York Heart Association (NYHA) cardiac function classification criteria, subjects with grade III or V cardiac dysfunction), myocardial infarction within 12 months or undergoing coronary angioplasty or stent placement, unstable angina pectoris, or electrocardiogram indicating a significantly prolonged QT interval (\>480ms) or the investigator determined severe arrhythmia;
* Had a history of head trauma, consciousness disorder, epilepsy, cerebrovascular ischemia, or cerebrovascular hemorrhagic disease, and required medication within the past 6 months;
* Had hepatitis B surface antigen (HBsAg) greater than 10E6 IU/mL at screening; positive hepatitis C virus (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis antibody; EBER positive or EBV copy number \> upper limit of normal;
* Those who require the use of steroid hormones during CAR-T infusion (except for those using inhaled steroid hormones locally); subjects who are receiving systemic steroid treatment before screening and whose study investigators determine that they need long-term systemic steroid treatment during the treatment period (excluding those using inhaled or local steroid hormones);
* Subjects with treatable autoimmune diseases, immunodeficiency or those requiring immunosuppressive therapy;
* Subjects who had acute graft-versus-host disease (GvHD) or moderate to severe chronic GvHD within 4 weeks before screening;
* Subjects with a history of allergy to any component of the cell product;
* Pregnant or lactating women, as well as male or female subjects who have reproductive capacity and cannot take effective contraceptive measures within 1 year after cell infusion (regardless of gender); male subjects who plan to conceive within 1 year after cell infusion; female subjects or their partners who plan to conceive within 1 year after cell infusion;
* Any situation that the investigator considers may increase the risk for the subject or interfere with the test results.

主要终点：Safety evaluation of Sup19 CAR-T cell therapy in patients with hematologic malignancies who have failed prior CD19-targeted therapy or exhibit weak CD19 expression: dose-limiting toxicity (DLT) adverse events (with particular focus on CRS and ICANS) · up to 28 after CAR-T cell infusion
次要终点：The best response rate of Sup19 CAR-T cell therapy within 3 months(The proportion of patients achieving CR/CRi)；Duration of response (DOR)；Event-free Survival, (EFS）；Leukemia-free Survival, (LFS）；The proportion of patients who received hematopoietic stem cell transplantation under the alleviated condition；Overall Survival,(OS）；Negative rate of Minimal Residual Disease（MRD）

• 3 dose groups · EXPERIMENTAL · Using a dose escalation and rapid titration design, the CAR-T dose groups were (1) 0.5×10\^6 CAR-T cells/kg; (2) 1×10\^6 CAR-T cells/kg; (3) 3×10\^6 CAR-T cells/kg.

Evaluation of Sup19 CAR-T cells in cases where previous CD19-targeted therapy has failed or where CD19 Evaluation of Safety and Efficacy in the Treatment of Low-Grade Hematological Malignancies: A Prospective, Single-Arm Clinical Study Research