CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Volunteer to participate in the clinical trial; Fully understand and are informed of this study and sign the informed consent form; Willing to follow and able to complete all trial procedures.
2. Age 18-75 years (inclusive), male or female.
3. Estimated survival \> 12 weeks.
4. Patients with relapsed or refractory AML as defined in the Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory Acute Myeloid Leukemia (Version 2023);
5. Flow cytometry or immunohistochemical examination of bone marrow or peripheral blood samples showed positive expression of CD38 in tumor cells and the expression rate was ≥80%.
6. ECOG score 0-2.
7. 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;
   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. The participant has any serious illness, laboratory abnormality, or psychiatric disorder that may impair the ability to receive or tolerate planned trial treatment; or the investigator judges that the participant's participation in the clinical trial is not in his/her best interest (e.g.,compromised health), or may hinder, limit, or confound protocol-specific Assessments.
2. Participants were diagnosed with acute promyelocytic leukemia (APL),BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase),secondary AML (other than MDS), central nervous system leukemia.
3. Participants with a history of epilepsy or other central nervous system disease;
4. Participants who have previously received autologous or allogeneic CAR-T therapy.
5. Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks.
6. Participants who have received prior immunotherapy targeting CD38.
7. Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD.
8. 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 Qinglin;
3. History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
4. History of severe nonischemic ardiomyopathy;
5. Other cardiac disease that the investigatorbelieve 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.

主要终点：MTD and/or dose range · Evaluate Dose limited toxicity and recommended dosage range after CT0991 infusion. · Up to 28 days after CAR-T cells infusion；Adverse Events (AE) after CT0991 infusion · An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria. · 12 months after CT0991 infusion；Dose-limiting toxicity （DLT） · The DLT is evaluated as the proportion of patients who experienced adverse events related to CT0991 that meet the criteria for DLT events after the first infusion. · Up to 28 days after CAR-T cells infusion.
次要终点：Complete response (CR), complete response with partial hematologic recovery (CRh)；Morphologic leukemia-free status (MLFS) and partial response (PR)；Duration of response （DOR)；Event-free survival (EFS)；Overall survival (OS)；Minimal Residual Disease (MRD) Negative Rate；Pharmacokinetic parameters of CT0991, including CAR copy number, peak value, AUC (area under the curve), in vivo persistence, etc.

• CAR-T cells# chimeric antigen receptor T cells# · EXPERIMENTAL · CT0991 CAR-T cels inffusicn

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients with Relapsed/Refractory Acute Myeloid Leukemia.