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

Phase 3

Recruiting

• Conditions: Newly Diagnosed Acute Myeloid Leukemia With High Risk
• Interventions: Drug: Standard Chemotherapy; Drug: HVA; Drug: VA

• Registration Number: NCT06810791
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2025-01-01
• Study First Submitted: 2025-01-16
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-04
• Last Update Submitted: 2025-02-04
• Study First Posted: 2025-02-06
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 876

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IC regiment for Fit-AML	Standard Chemotherapy	-
HVA regiment for unfit-AML	HVA	-
HVA regiment for Fit-AML	HVA	-
VA regiment for unfit-AML	VA	-

Primary Outcome Measures

Name	Time	Method
Composite complete remission (CRc)	At the end of cycle 2 (each cycle is 28 days).	CRc includes complete remission (CR) and complete remission accompanied with with incomplete count recovery (CRi).

Secondary Outcome Measures

Name	Time	Method
Complete remission (CR)	At the end of cycle 2 (each cycle is 28 days).	Complete remission is defined as BM with \>5% blasts and without extramedullary infltration and recovery of peripheral blood cells.
Overall response rate (ORR)	At the end of cycle 2 (each cycle is 28 days).	ORR includes CRc, partial response (PR), and morphologic leukemia-free state (MLFS).
DOR	1 year	duration of response
Rate of Measurable residual disease (MRD) negative	At the end of cycle 2 (each cycle is 28 days).	MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%.
Overall survival (OS)	1 year	OS is calculated from enrollment to death or the last follow-up.
Event-free survival (EFS)	1 year	EFS is calculated from enrollment to the date of relapse or death or the last follow-up.
Adverse events (AE)	The first dose until 28 days after treatment discontinuation	AE are recorded from the first dose until 28 days after treatment discontinuation and are graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0.

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China