HVA vs IA/DA or VA in the Treatment of ND HR-AML

Nanfang Hospital, Southern Medical University

Status and phase: Enrolling; Phase 3

Conditions: Newly Diagnosed Acute Myeloid Leukemia With High Risk

Treatments: Drug: Standard Chemotherapy; Drug: VA; Drug: HVA

Study type: Interventional

Funder types: Other

Identifiers

NCT06810791

NFEC-2024-576

Details and patient eligibility

About

The aim of this study is to evaluate the safety and efficacy of homohartonine combined with venetoclax and azacitidine (HVA) versus intensive chemotherapy (IA/DA) or venetoclax combined with azacitidine (VA) in newly diagnosed high-risk AML patients.

Full description

The HVA regimen exerts a synergistic pro-apoptotic effect and has demonstrated significant clinical efficacy against R/R AML and also overcomes adaptive resistance observed in the VA regimen. Exploratory work with small sample sizes in first-line settings suggests that combination of HHT and Ven+AZA exhibits potent anti-AML effects with good safety profiles, particularly in overcoming the impact of high-risk factors associated with AML relative to standard treatments. This indicates its potential as a more ideal option for the treatment of newly diagnosed AML with high risk factors. Therefore a prospective, multi-center, randomized controlled clinical study is planned to evaluate the efficacy and safety of the HVA regimen compared to intensive chemotherapy (IA/DA) or Venetoclax plus azacitidine (VA) regimens in newly diagnosed high-risk fit-AML or unfit AML patients.

Enrollment: 876 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• According to the world health organization (WHO) classification of newly diagnosed with AML patients;
• Age ≥18 years old;
• High-risk patients should meet any of the following criteria: ① High risk group according to the European Leukemia Risk stratification (ELN) 2022; (2) Secondary AML (sAML) which develops from myelodysplastic syndrome (MDS), bone marrow hyperplastic tumor (MPN) or chronic myeloid cell leukemia, et.; (3) Treatment-related AML (t-AML), Patients have a history of cytotoxic treatment record or ionizing radiation therapy.
• Patients did not receive anti-AML therapy (except leukopenia therapy, such as hydroxyurea or cytarabine < 1.0g/d) after the diagnosis of AML;
• Expected survival ≥12 weeks;
• The eastern tumor cooperation group (ECOG) score 3 points or less;
• Kidney function: creatinine clearance acuity 30 ml/min;
• Liver function: ALT < 5 times normal value, bilirubin < 3 times normal value;
• Sign the informed consent form and understand and abide by the plan calls for process.

Exclusion criteria

• Acute promyelocytic leukemia;
• With central nervous system leukemia (CNSL) ;
• The cardiac function > level 2;
• The AIDS virus (HIV) infection;
• Other clinical significance of uncontrolled condition, including but not limited to: (1) out of control, or active systemic infection (viruses, bacteria or fungi); (2) chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; (3) need to actively deal with the merger of the second tumor;
• Can't take oral treatment or having a gastrointestinal disease impact ing the absorption;
• Being allergy to the experimental drugs;
• Pregnant and lactating women;
• Patients who could not understand or adhere to the study protocol;
• Patients deemed by the investigator to be ineligible for enrollment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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876 participants in 4 patient groups

IC regiment for Fit-AML

Active Comparator group

Treatment:

Drug: Standard Chemotherapy

HVA regiment for Fit-AML

Experimental group

Treatment:

Drug: HVA

VA regiment for unfit-AML

Active Comparator group

Treatment:

Drug: VA

HVA regiment for unfit-AML

Experimental group

Treatment:

Drug: HVA