CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
2. Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2016-WHO criteria. Participants should not be treated with any kind of TKIs or chemotherapy.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and expected survival period ≥ 3 months.
4. Organ function as indicated by the following laboratory indicators must be met:

1\. Alanine aminotransferase (ALT) ≤ 5×upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 5×ULN; 2. Total bilirubin\<2×ULN; 3. 24-hour calculated creatinine clearance\>30 mL/min; 4. SpO2≥92%; 5. Cardiac ejection fraction (EF)≥40%;

Exclusion Criteria:

1. Active hepatitis B virus (defined as serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Subjects with HBV-DNA \< 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.) ;
2. Uncontrolled active infection;
3. Patients who are currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS;
4. Patients who have any history of heart or vascular disease, such as hypertension (systolic blood pressure(HBP) \> 140mmHg and/or diastolic blood pressure \> 90mmHg);
5. Cardiac ultrasonography indicates that pulmonary artery systolic blood pressure is \>50 mmHg; or there are clinical symptoms related to pulmonary arterial hypertension;
6. Patients who suffer from severe bleeding disorders unrelated to Ph+ ALL;
7. Patients who have any other malignant tumors that require treatment;
8. Patients who have severe hypertriglyceridemia (triglyceride ≥ 5.6mmol/L);
9. Patients who are pregnant, planning to become pregnant or breastfeeding;
10. Patients who underwent major surgery (except for minor surgery such as catheter placement or bone marrow biopsy) within 14 days before the first drug;
11. Patients who may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or fail to comply with all required study procedures;
12. Patients who suffer from any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the safety of the research drug.

主要终点：Number of Participants with Complete Molecular Remission · Will be estimated along with the 95% credible intervals. Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%. · 3 months；Incidence of adverse events (AEs) · Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval. · 2 years
次要终点：Objective Response Rate (ORR)；Duration of Complete Molecular Remission；Event-free survival (EFS)；Overall survival (OS)

• Treatment Group · EXPERIMENTAL · ThisCART19A cells infusion, Given intravenously，Combined With Olverembatinib, Given PO

This is an Open, Prospective, Single-arm Study, which is designed to evaluate the efficacy, safety and pharmacokinetics of ThisCART19A Combined With Olverembatinib for the treatment of Newly Diagnosed Ph-positive lymphoblastic leukemia.