CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Aged 18 \~ 70 years old (including boundary value), regardless of gender;
2. FLT-3 positive acute myeloid leukemia;
3. The expected survival time was more than 3 months;
4. ECOG score 0-2;
5. Refractory or relapsed AML patients after standardized treatment who meet any of the following criteria:

   1. After complete remission (CR), there were ≥5% leukemia cells or blast cells in the bone marrow(except for other reasons such as bone marrow regeneration after consolidation chemotherapy)in the peripheral blood and extramedullary lesions;
   2. Naive patients who are treated with 2 courses of treatment and are ineffective;
   3. Those who have relapsed within 12 months after CR after consolidation and intensive treatment;
   4. Those who relapse after 12 months but are ineffective after conventional chemotherapy;
   5. Subjects who experienced relapses twice or multiple times; with persistent extramedullary leukemia.
6. Kidney function, cardiopulmonary function, liver function, and coagulation function meet the following requirements:

   1. Creatinine ≤ 1.5 ULN;
   2. Left ventricular ejection fraction ≥ 50% and echocardiography does not reveal pericardial effusions and ECG does not reveal clinically significant abnormal bands;
   3. Blood oxygen saturation \> 92%;
   4. Total bilirubin ≤ 2 × ULN; ALT and AST ≤ 2.5 × ULN; for the patients with ALT and AST abnormalities caused by disease which researchers judge (e.g. liver infiltrates or bile duct obstruction), the indicators of which can be relaxed to ≤5× ULN;
   5. PT/INR and PTT ≤ 1.5 ULN;
7. Patients understand the trial and have signed the informed consent form.

Exclusion Criteria:

1. Patients with malignant tumors other than acute myeloid leukemia within 5 years before the screening, except fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after the radical operation, and breast ductal carcinoma in situ after radical operation;
2. Patients with hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference range; Hepatitis C virus (HCV) antibody positive and hepatitis C virus (HCV) RNA positive in peripheral blood; Human immunodeficiency virus (HIV) antibody-positive; Cytomegalovirus (CMV) DNA positive; Syphilis test positive;
3. Patients with severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade III), severe arrhythmia;
4. Patients with unstable systemic diseases judged by the researcher: including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment;
5. Within 7 days before screening, there were active or uncontrollable infections requiring systemic treatment (except mild urogenital infection and upper respiratory tract infection);
6. Pregnant or lactating women, female subjects who planned pregnancy within 2 years after cell reinfusion, or male subjects whose partners planned pregnancy within 2 years after cell reinfusion;
7. Subjects who were receiving systemic steroid treatment within 7 days before screening or who were determined by the investigator to need long-term systemic steroid treatment during treatment (except inhalation or local use);
8. Participated in other clinical studies within 1 month before screening;
9. There was evidence of central nervous system invasion during subject screening(e.g. detection of tumor cells in cerebrospinal fluid or imaging suggests central infiltrates;);
10. Patients with graft-versus-host disease (GVHD) or requiring immunosuppressive agents;
11. Patients with a history of epilepsy or other central nervous system disorders;
12. Patients with primary immunodeficiency diseases;
13. Patients who are not suitable for cell construction judged by researchers;
14. Other situation researchers believe that it is not suitable for inclusion.

主要终点：Maximal tolerable dose (MTD) · Fludarabine + Cyclophosphamide + TAA05 Cell Injection Patients will receive lymphodepletion with fludarabine (25 mg/kg) and cyclophosphamide (250 mg/kg) for 3 days on day -7\~-2, followed by the infusion of TAA05 Cell with the dose of 1×10\^8, 2×10\^8 or 4×10\^8 cells on day 0. If no dose-limited toxicity(DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. MTD is defined as the highest dose at which DLT occurs in no more than 2 of the 6 patients. After the end of dose climbing, if the maximum dose group(MTD) is still not observed, the highest dose group is defined as MTD. · within 2 yeas after infusion
次要终点：Incidence of Treatment-related Adverse Events；Overall response rate(ORR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia；Complete response rate(CRR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia；Overall survival(OS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia；Progress-free survival(PFS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia；Duration of Response(DOR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia；In vivo expansion and survival of Anti-FLT3 CAR-T Cell

• TAA05 Cell Injection · EXPERIMENTAL · Fludarabine + Cyclophosphamide + TAA05 Cell Injection Patients will receive lymphodepletion with fludarabine (25 mg/kg) and cyclophosphamide (250 mg/kg) for 3 days on day -7\~-2, followed by the infusion of TAA05 Cell with the dose of 1×10\^8, 2×10\^8 or 4×10\^8 cells on day 0. If no dose-limited toxicity(DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. After the end of dose climbing, if the maximum dose group(MTD) is still not observed, the highest dose group is defined as MTD.

This is a clinical trial of Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the treatment of patients with relapsed / refractory acute myeloid leukemia. The purpose is to evaluate the safety and efficacy of anti-FLT3 CAR-T cells in patients with relapsed / refractory acute myeloid leukemia.