Allogeneic CAR-T(CT0890B) in NKG2DL+ R/R AML

A Phase I Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Cells (CT0890B) in Patients With NKG2DL-Positive Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study to Investigate the Safety and Efficacy of CT0890B in Patients with Relapsed/Refractory Acute Myeloid Leukemia.

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, efficacy, and cellular pharmacokinetics of CT0890B in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 12~27 participants in this trial.

Inclusion Criteria:

1. Age 18-70 years (inclusive), male or female.

2. Relapsed or refractory acute myeloid leukemia (R/R AML) diagnosed according to the 2022 World Health Organization classification or ELN criteria, with confirmed NKG2D ligand-positive disease.

3. Bone marrow blasts ≥5% by morphology.

4. Estimated life expectancy >12 weeks.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

6. Adequate organ function without ongoing supportive care, defined as:

   1. Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
   2. Hepatic: ALT and AST ≤2.5 × upper limit of normal (ULN), and total bilirubin ≤2 × ULN;
   3. Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula);
   4. Coagulation: activated partial thromboplastin time (APTT) ≤1.5 × ULN and prothrombin time (PT) ≤1.5 × ULN.

   c) Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula); d) Coagulation: 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), 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 NKG2DL;
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 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;