Safety and Efficacy Study of CI-135 CAR-T Cells in Subjects with Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

1. Age ≥5 years old and ≤70 years old, male or female;

2. Expected survival exceeds 12 weeks;

3. Diagnosed as primary or secondary AML patients that meet the World HealthOrganization (WHO) classification, and meet any of the following conditions: a) AMLpatients who have not reached complete remission after at least 3 cycles of standardinduction chemotherapy B) AML patients who have achieved complete remission afterinduction chemotherapy and relapse within 1 year; c) AML patients who have relapsedafter achieving complete remission after induction chemotherapy for more than 1 yearand have not remitted after 1 course of induction chemotherapy; d) AML patients whohave relapsed after transplantation ; E) AML patients who have experienced 2 or morerelapses. For patients who meet one of a), b), and c) and have FLT-3 mutations, inaddition to induction therapy, they should also receive at least one TKI treatmentand has not achieved complete remission or relapsed after complete remission (exceptpatients who cannot tolerate TKI treatment or have contraindications to TKItreatment).

4. The FLT-3 mutation is positive by the leukemia cell gene detection, or the FLT-3expression is ≥35%;

5. ECOG score 1-2;

6. Liver, kidney, heart and lung functions meet the following requirements:

7. Glomerular filtration rate ≥60 ml/min/1.73 m2 or serum creatinine ≤2 times theupper limit of normal;

8. Serum AST, ALT≤3 times the upper limit of normal, and total bilirubin≤1.5 timesthe upper limit of normal;

9. Blood oxygen saturation> 92%;

10. The ventricular ejection fraction ≥50%, there is no pericardial effusiondetected by ultrasound, and no clinically significant ECG changes.

11. Able to understand this experiment and sign the informed consent form.

Exclusion Criteria:

1. Diagnosed as acute promyelocytic leukemia (APL M3);

2. Accompanied with other uncontrolled malignant tumors (except those that would notinterfere with the safety or efficacy evaluation of the trial).

3. Have received CAR-T cell or other genetically modified cell therapy in the past;

4. Medical history or evidence of significant cardiovascular risk, including any of thefollowing conditions: congestive heart failure, unstable angina, clinicallysignificant arrhythmia (such as ventricular fibrillation, ventricular tachycardia,etc.), performed coronary angioplasty 6 months before infusion, intracardiacdefibrillator or any clinically-related complications that may pose a risk to thesafety of the subject or interfere with the evaluation, procedures or completion ofthe research;

5. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis Bcore antibody (HBcAb) and whose peripheral blood HBV DNA titer test is greater thanor equal to the lower limit of detection; those who are positive for hepatitis Cvirus (HCV) antibody and positive for peripheral blood HCV RNA; Humanimmunodeficiency virus (HIV) antibody positive; syphilis test positive;

6. Acute or chronic hepatitis C is positive. Exceptions: acute hepatitis C withcomplete clearance of the virus; chronic hepatitis C, with a sustained virologicalresponse 24 weeks after completion of hepatitis C treatment (SVR24) determined anundetectable viral load;

7. A history of arterial or venous thrombosis within 3 months before enrollment;

8. Any graft-versus-host disease that requires systemic application ofimmunomodulators;

9. A history of central nervous system disease or subjects who need treatment (forexample, uncontrolled seizures);

10. Active infection that cannot be controlled.

11. Subjects who are known to be allergic to the components of CI-135 CAR-T cells or anycomponents of the lymphodepletion regimen (cyclophosphamide and fludarabine).

12. Women who are pregnant or breastfeeding, and female patients who plan to becomepregnant within 1 year after cell infusion, or male patients whose partners plan tobecome pregnant within 1 year after their infusion.

13. Other situations that are considered to be unsuitable to participate in the study byresearchers.