CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Age 18-70 years (inclusive), male or female
2. Relapsed or refractory acute myeloid leukemia definitively diagnosed as CLL-1 positive according to the WHO 2022 classification
3. Bone marrow blast percentage ≥5% by morphology
4. Estimated survival \> 12 weeks
5. ECOG score 0-2
6. Participants should meet the following test results (no ongoing supportive care)

   1. Left ventricular ejection fraction (LVEF) \> 50%
   2. ALT≤ 2.5 × ULN, AST ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN; ALT≤ 5 × ULN, AST ≤ 5 × ULN, total bilirubin ≤ 3 × ULN, if the liver is involved
   3. Endogenous creatinine clearance ≥ 30 mL/min (creatinine clearance calculated using the Cockcroft-Gault formula)
   4. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN and prothrombin time (PT) ≤ 1.5 × ULN

Exclusion Criteria:

1. Participants were diagnosed with acute promyelocytic leukemia (APL) BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), active central nervous system leukemia
2. Participants with a history of epilepsy or other central nervous system disease
3. Participants who have previously received autologous or allogeneic CAR-T therapy
4. Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks
5. Participants who have received prior immunotherapy targeting CLL-1
6. Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD
7. Participant has any of the following at screening:

1)Active, uncontrolled systemic infection or requiring intravenous anti-infective agents 2)Any of the following cardiac conditions, including:

1. New York Heart Association Class III-IV heart failure;
2. History of myocardial infarction, coronary artery bypass grafting, or unstable angina within 6 months prior to Lymphodepleting Chemotherapy;
3. History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
4. History of severe non-ischemic cardiomyopathy;
5. Other cardiac disease that the investigator believe could jeopardize the participant 's well-being or compromise participation in this clinical trial; 3) Active bleeding of clinical significance as judged by the investigator 4)Requiring supplemental oxygen to maintain oxygen saturation\> 92% 5)Patients with severe chronic obstructive pulmonary disease (COPD) or other lung diseases that cannot tolerate CAR-T treatment as judged by the investigator 8. Has HIV, syphilis infection, active hepatitis B virus infection (HBsAg positive and HBV-DNA above the detection limit), or active hepatitis C virus infection (HCV antibody and HCV-DNA positive)

主要终点：Adverse Events (AE) after CT1390B infusion · An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria · 12 months after CT1390B infusion；Dose-limiting toxicity （DLT） · The DLT is evaluated as the proportion of patients who experienced adverse events related to CT1390B that meet the criteria for DLT events after the first infusion · Up to 28 days after CAR-T cells infusion；MTD and/or dose range · Evaluate Dose limited toxicity and recommended dosage range after CT1390B infusion · Up to 28 days after CAR-T cells infusion
次要终点：Complete response (CR), complete response with partial hematologic recovery (CRh)，and complete response with incomplete hematologic recovery (CRi)；Morphologic leukemia-free status (MLFS) and partial response (PR).；Proportion of patients undergoing stem cell transplantation following CAR-T therapy.；Duration of response (DOR)；Event-free survival (EFS)；Overall survival (OS)；Minimal Residual Disease (MRD) Negative Rate；Cmax

• CT1390B CAR-T cells Injection · EXPERIMENTAL · CAR-T cells#chimeric antigen receptor T cells#CT1390B cells infusion

A Clinical Study to Investigate the Safety and Efficacy of CT1390B in Patients with Relapsed/Refractory Acute Myeloid Leukemia