Acute myeloid leukemia (AML)
Conditions
Interventions
Low dose trial group:SKIC-02 injection, 2 mg/dose, intravenous infusion on D0, D2, and D4
High dose experimental group:SKIC-02 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 comply with the protocol requirements; 2. No gender restriction; 3. Age: >=18 years old and =3 months; 5. Subjects with pathologically confirmed relapsed/refractory intermediate-to-high risk AML meeting the 2016 (Revised) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, or AML subjects who are intolerant to other drug treatments (e.g., drug-related >=Grade 3 toxicity leading to permanent treatment discontinuation during treatment) and for whom the investigator determines no other appropriate treatment options are available; 6. Patients meeting the definition of relapsed/refractory acute myeloid leukemia according to Chinese Guidelines for Diagnosis and Treatment of Relapsed/Refractory Acute Myeloid Leukemia (2023 Edition): (1) Diagnostic criteria for relapsed AML: Leukemia cells reappear in peripheral blood, or blast cells >=5% in bone marrow (excluding other causes such as bone marrow regeneration after consolidation chemotherapy), or extramedullary leukemia infiltration occurs after complete remission (CR) of AML. (2) Diagnostic criteria for refractory AML: De novo patients who fail to respond to two courses of standard regimen treatment; patients who relapse within 12 months after CR following consolidation and intensive therapy; patients who relapse after 12 months and fail to respond to conventional chemotherapy; patients with two or more relapses; patients with persistent extramedullary leukemia. 7. Morphological assessment shows bone marrow blast cells >=5%; 8. Flow cytometry detection of bone marrow or peripheral blood samples shows positive expression of CLL1 and/or FLT3; 9. Eastern Cooperative Oncology Group (ECOG) performance status score =50 mL/min (in accordance with the calculation standard of the study center); (3) Coagulation function: International normalized ratio (INR) <=1.5, and activated partial thromboplastin time (APTT) <=1.5 ULN; (4) Urine protein <=2+ or <=1000 mg/24h; 12. Premenopausal women of childbearing potential must undergo a serum/urine pregnancy test within 7 days prior to treatment initiation with a negative result, and must not be lactating. All enrolled patients (regardless of gender) must adopt adequate barrier contraceptive measures throughout the treatment period and for 6 months after treatment completion.
Exclusion criteria
Exclusion criteria: 1. Presence of other uncontrolled malignant tumors; 2. Prior receipt of chimeric antigen receptor T-cell (CAR-T) therapy targeting any AML-associated antigens (including CD33, CD123, etc.), or bispecific antibody (BiTE) targeting AML-associated antigens and T-cell CD3 antigen, with an interval of less than 6 months from the first administration; 3. Acute promyelocytic leukemia, Ph+ acute myeloid leukemia (AML), AML transformed from blast crisis of chronic myeloid leukemia, myelodysplastic syndrome (MDS), or myeloproliferative neoplasm (MPN); or patients with low-risk relapsed AML who have received only second-line treatment; 4. Administration of chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by investigator), targeted therapy (including small-molecule tyrosine kinase inhibitors) and other anti-tumor therapies within 4 weeks prior to the first administration or within 5 half-lives (whichever is shorter); or administration of palliative radiotherapy, modern proprietary Chinese medicines approved by NMPA for anti-tumor treatment within 2 weeks prior to the first administration; 5. Receipt of major surgical treatment or significant traumatic injury within 4 weeks prior to the first dose (excluding percutaneous biopsy, endoscopic biopsy, etc.); 6. History of severe cardiovascular and cerebrovascular diseases within 6 months before screening, including but not limited to: left ventricular ejection fraction =Grade 2 (CTCAE v5.0), NYHA Class >=2 heart failure, history of myocardial infarction, cerebral vascular accident, transient ischemic attack (TIA), cerebral infarction, etc.; 7. Prolonged QT interval (male QTcF >450 msec or female QTcF >470 msec), complete left bundle branch block, third-degree atrioventricular block, frequent and uncontrollable arrhythmias (e.g. atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter; excluding transient atrial fibrillation/atrial flutter); 8. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc. Exclusions: type I diabetes mellitus, hypothyroidism controlled by replacement therapy only, skin diseases without need for systemic treatment (e.g. vitiligo, psoriasis); 9. History of extensive intestinal resection, or presence of Crohn's disease, ulcerative colitis, chronic diarrhea, intestinal obstruction; 10. Diagnosis of other malignant tumors within 5 years prior to the first administration, except for: cured basal cell carcinoma of skin, cured squamous cell carcinoma of skin, and/or radically resected carcinoma in situ; 11. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg); 12. Pulmonary diseases >=Grade 3 as defined by CTCAE v5.0, history of interstitial lung disease (ILD) requiring systemic steroid therapy, or current interstitial lung disease; 13. Patients with central nervous system involvement; 14. Patients with extramedullary involvement; 15. Known hypersensitivity to the study drug and its excipients; 16. Prior solid organ transplantation; or autologous hematopoietic stem cell transplantation within 3 months. (1) Patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 6 months before screening are excluded; (2) Patients with act
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT) and its incidence rate Type:Primary indicator;Frequency and severity grading of Adverse Events (AEs) and Serious Adverse Events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) per ELN criteria;Duration of Response (DOR), Progression-Free Survival (PFS), Overall Survival (OS) Type:Secondary indicator;Pharmacokinetic (PK) parameters (Cmax, Tmax, t1/2, AUC);Pharmacodynamic (PD) characteristics (changes in CLL1/FLT3 positive leukemia cells, CAR expression on T cells);Immunogenicity (incidence and titers of ADA and Nab); | — |
Countries
China
Contacts
Public ContactNiu Ting
West China Hospital, Sichuan University
Outcome results
None listed