Acute myeloid leukemia (AML)
Conditions
Interventions
Low dose experimental group:YMN-C01 injection, 2 mg/dose, intravenous infusion on D0, D2, and D4
High dose experimental group:YMN-C01 injection, 4 mg/dose, intravenous infusion on D0, D2, and D4.
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent and follow the requirements of the protocol; 2. No gender limit; 3. Age: >=18 years old and =3 months; 5. Subjects with pathologically confirmed relapsed/refractory intermediate-high risk AML according to the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues 2016 (revision) criteria, Or subjects with AML who are intolerant to other drug therapy (e.g., drug-related grade =3 toxicity during treatment leading to permanent discontinuation) and who have no other appropriate treatment as judged by the investigator; 6. According to the Chinese Guidelines for the diagnosis and treatment of relapsed/refractory acute myeloid leukemia (2023 edition), patients who meet the definition of relapsed/refractory acute myeloid leukemia: 1) Relapsed AML was defined as the presence of recurrent leukemia cells in peripheral blood or blasts in bone marrow (=5%) after complete remission (CR) of AML (except for other reasons such as bone marrow regrowth after consolidation chemotherapy) or extramedullary leukemia cell infiltration. 2) Refractory AML diagnostic criteria: newly diagnosed patients who failed to response to two courses of standard chemotherapy; Patients who relapsed within 12 months after consolidation and intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia. 7. Relapsed/refractory AML is defined as one of the following: 1) newly diagnosed patients who failed to respond to two courses of standard therapy; 2) relapsed within 12 months after consolidation and intensive therapy; 3) relapsed after 12 months but failed to respond to conventional chemotherapy; 4) two or more recurrences; 5) patients with relapsed or refractory acute myeloid leukemia who were not or unsuitable/intolerant to other therapies according to the investigator's judgment. 8. Bone marrow blasts should be >=5%. Flow cytometric analysis of bone marrow or peripheral blood samples positive for LILRB4 and/or LILRB3; 10. ECOG = 50 mL/min (according to the center's calculation criteria); 3) coagulation function: international normalized ratio (INR) <=1.5 and activated partial thromboplastin time (APTT) <=1.5ULN; 4) proteinuria <=2+ or <=1000mg/24h; 13. Fo
Exclusion criteria
Exclusion criteria: Patients were not eligible if they met any of the following criteria: 1. Accompanied by other uncontrolled malignant tumors; 2. Prior treatment with chimeric antigen receptor therapy or other transgenic T cells less than 6 months after the first dose; 3. Acute promyelocytic leukemia, or ph+AML, acute transformation of chronic myeloid leukemia or AML transformed from MDS (myelodysplastic syndrome) or MPN (myeloproliferative neoplasm); Or low-risk relapsed AML patients who had received only second-line therapy; 4. Antineoplastic therapy such as chemotherapy, biologic therapy, immunotherapy, definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks or 5 half-life cycles (whichever is shorter) before the first dose; Or palliative radiotherapy or modern traditional Chinese medicine preparations approved by NMPA for anti-tumor treatment within 2 weeks before the first dose; 5. Major surgical treatment or obvious traumatic injury (excluding needle biopsy, endoscopic biopsy, etc.) within 4 weeks before the first medication; 6. History of severe cardiovascular or cerebrovascular disease within 6 months before screening, such as: Left ventricular ejection fraction =grade 2 (CTCAE v5.0), New York Heart Association (NYHA) >= grade 2, history of myocardial infarction, unstable angina pectoris, acute coronary syndrome, myocardial infarction, cerebrovascular accident, transient ischemic attack (TIA), cerebral infarction; 7. Prolonged QT interval (QTcF > 450 msec in male or > 470 msec in female), complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia, such as atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter (except transient atrial fibrillation and atrial flutter); 8. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis); 7. History of extensive bowel resection or Crohn's disease, ulcerative colitis, chronic diarrhea, intestinal obstruction; 8. Patients with eosinophilia above the normal range and a history of severe allergic diseases or anaphylaxis; Patients with eosinophil-related disorders. 9. Other malignancies diagnosed within 5 years before the first dose, except for radical basal cell carcinoma, squamous cell carcinoma, and/or radical resection carcinoma in situ; 10. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg); 11. Patients with grade >=3 lung disease according to CTCAE v5.0, a history of interstitial lung disease (ILD) requiring systemic steroid therapy, or current ILD; 12. Patients with central nervous system involvement; 13. Patients with extramedullary invasion; 14. Known to be allergic to the study drugs and excipients; 15. Prior solid organ transplantation; Or had received autologous stem-cell transplantation within 3 months. The inclusion and exclusion criteria for patients with relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were as follows: patients who received allo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT) and its incidence rate;Frequency and severity grading of Adverse Events (AEs) and Serious Adverse Events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) per ELN criteria;Pharmacokinetic (PK) parameters (Cmax, Tmax, t1/2, AUC);Pharmacodynamic (PD) characteristics (changes in LILRB3/4 positive leukemia cells, CAR expression on T cells);Immunogenicity (incidence and titers of ADA and Nab); | — |
Countries
China
Contacts
Public ContactTing Niu
West China Hospital, Sichuan University
Outcome results
None listed