Acute myeloid leukemia (AML)
Conditions
Interventions
Control Group:Venetoclax: 100mg on d1, 200mg on d2, 400mg on d3-28 (dose escalation) in cycle 1
400mg/d continuous administration starting from cycle 2. Azacitidine: 75 mg/m2/d subcutaneously on d1-7.
Trial Group:Venetoclax: 100mg on d1, 200mg on d2, 400mg on d3-28 (dose escalation) in cycle 1
400mg/d continuous administration starting from cycle 2. Azacitidine: 75 mg/m2/d subcutaneously on d1-7. Homoharringtonine (HHT): 1 mg/m2/d intravenously infused on d1-7.
Sponsors
Shanghai General Hospital
Eligibility
Sex/Gender
All
Age
60 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Diagnosed with acute myeloid leukemia (AML), excluding acute promyelocytic leukemia (APL), according to the 2022 International Consensus Classification (ICC). 2.Age between 60 and 75 years, regardless of sex. 3.Estimated life expectancy of at least 12 weeks. 4.Eastern Cooperative Oncology Group (ECOG) performance status of 0–3. 5.Adequate organ function, defined as follows (unless abnormalities are attributable to leukemia involvement): Serum creatinine 92%; Total bilirubin <=3 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 × ULN; (If abnormalities are considered leukemia-related, total bilirubin <=5 × ULN and ALT/AST <=5 × ULN are allowed). 6.Female participants of childbearing potential must be postmenopausal or surgically sterile. Male participants must agree to use effective contraception or refrain from sperm donation during the study and for at least 90 days after the last dose. 7.Participants must be able to understand the study procedures, voluntarily participate, and provide written informed consent prior to enrollment.
Exclusion criteria
Exclusion criteria: 1.Prior treatment with any of the following: Hypomethylating agents or any chemotherapy for myelodysplastic syndrome (MDS) (except hydroxyurea); Chimeric antigen receptor T-cell (CAR-T) therapy or other investigational treatments. 2.History of myeloproliferative neoplasm (MPN). 3.Patients classified as favorable-risk AML according to the 2022 European LeukemiaNet (ELN) guidelines. 4.Known active central nervous system (CNS) involvement by AML. 5.Known human immunodeficiency virus (HIV) infection. 6.Active hepatitis B or C infection requiring antiviral therapy, or risk of hepatitis B virus (HBV) reactivation (HBsAg-positive or HBcAb-positive without antiviral prophylaxis). 7.History of malignancy other than myeloid neoplasms within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer after curative treatment, or ductal carcinoma in situ. 8.Any unstable systemic disease, including but not limited to: Myocardial infarction, stroke, or transient ischemic attack within 3 months prior to screening; Congestive heart failure (NYHA class >= III); Clinically significant or uncontrolled arrhythmias or prolonged QTc interval (>=470 ms for males, >=480 ms for females); Severe cardiovascular disease requiring ongoing treatment; Severe hepatic, renal, or metabolic disorders; Pulmonary hypertension. 9.Malabsorption syndrome or any condition that precludes oral administration of study drugs. 10.Active systemic infection requiring treatment (including bacterial, viral, or fungal infections). 11.Clinically significant neurological or psychiatric disorders requiring treatment, including >= grade 2 epilepsy, paralysis, aphasia, recent cerebral infarction, severe traumatic brain injury, dementia, Parkinson’s disease, or schizophrenia. 12.Participants of reproductive potential unwilling to use effective contraception during the study and for 12 months after the last dose. 13.White blood cell (WBC) count >25 × 10?/L (hydroxyurea is permitted to control WBC to meet eligibility criteria).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite Complete Remission Rate (CRc); | — |
Secondary
| Measure | Time frame |
|---|---|
| Event-Free Survival (EFS);Overall Survival (OS);Time to First Composite Complete Remission;Composite Complete Remission Rate by the Start of the 2nd/3rd Treatment Cycle;Complete Remission Rate (CR);Measurable Residual Disease-Negative Rate (MRD-);Safety Outcomes (including Adverse Events, Serious Adverse Events, Death Events, Laboratory Values, Vital Signs); | — |
Countries
China
Contacts
Public ContactJia Yanan
Shanghai General Hospital
Outcome results
None listed