CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Patients must satisfy the following criteria to be enrolled in the study.

1. Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed consent form (ICF).
2. Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted.
3. Patient has eligible disease status:

   3.1 Primary or Secondary acute myeloid leukemia (AML) Patients in first of second Morphological Complete Remission (CR), Morphological Complete Remission with incomplete hematologic recovery (CRi), or Morphologic Leukemia-free State (MLFS) as defined by the European LeukemiaNet (ELN) recommendations for AML Response Criteria (Dohner, 2017).

   3.2 R/R diagnosis based on confirmed diagnosis with local pathology report following any reinduction/ salvage therapy ELN guidelines.

   3.2.1 Relapsed AML are defined as having relapsed after achieving ≥ 1 CR, including relapse after allogeneic stem cell transplantation (≥ 2 months after transplant).

   3.2.2 Refractory AML, defined as not achieving CR, CRi, or MLFS after 2 or more cycles of induction therapy (primary refractory) or not achieving CR after treatment for relapsed AML.

   3.2.3 Secondary AML (MDS transformation): Secondary AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.

   3.2.4 Treatment-related AML: Treatment-related AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.
4. No active infection.
5. No heart , liver and kidney functioninsufficiency.
6. No central nervous system leukemia.

Exclusion Criteria:

1. Subject meets one of the following criteria. 1.1History of CAR-T treatment with third degree CRS. 1.2 History of NK cell and CIK cell immunotherapy.
2. Serious cardiovascular and cerebrovascular diseases. 2.1 Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms.

   2.2 Complete left bundle branch block, second- or third-degree atrioventricular block; 2.3 Severe, uncontrolled cardiac arrhythmias requiring medication. 2.4 New York Heart Association (NYHA) class II or above congestive heart failure.

   2.5 Left ventricular ejection fraction (LVEF) \<50% in color Doppler echocardiography.

   2.6 History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, severe pericardial disease, ECG evidence of acute ischemic or active conduction system abnormalities within 6 months prior to recruitment.
3. Previous or present concomitant other malignancies (except for basal cell carcinoma of the skin, non-melanoma and non-melanoma, carcinoma in situ of the breast/cervix that have been effectively controlled, and other malignancies that have been effectively controlled without treatment in the past five years).
4. Uncontrollable systemic disease(e.g. uncontrolled hypertension, diabetes, etc).
5. Pregnant women, lactating females, patients who refuse to use effective contraception during the study.
6. history of severe neurological or psychiatric illness.
7. Positive for hepatitis B surface antigen.
8. Patients who are judged by the investigator to be unsuitable for participating in this study.

主要终点：Incidence of Treatment-Emergent Adverse Events · 12 months；MRD negative rate · 12 months；Progression-free Survival · 12 months；Overall survival · 12 months
次要终点：Determination of chimerism of iNK cells in peripheral blood of subject.

• Cell therapy group · EXPERIMENTAL · Intravenous infusion of iNK cells is given to the subject, 5\*108 to 1\*109 cells/dose, two doses per week, a total of 8 doses. And then 1\*109 cells/dose, one doses every 4 weeks , a total of 5 doses.

This is a clinical study on the use of iNK cells for the treatment of refractory relapsed acute myeloid leukemia.