Clinical trial NCT06810791: HVA vs IA/DA or VA in the Treatment of ND HR-AML
Official title: The Efficacy and Safety of Homoharringtonine Combined With Venetoclax and Azacitidine Versus Standard Chemotherapy or VA in the Treatment of Acute Myeloid Leukemia With High-risk, a Multicenter, Prospective, Randomized Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Newly Diagnosed Acute Myeloid Leukemia With High Risk
Keywords: HVA regimen
Intensive chenmotherapy
Fit
randomized controlled trial
Phase 3
VEN combined with AZA
Unfit
Newly diagnosed
High risk
Acute myeloid leukemia
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Guangzhou First People's Hospital
name: Guangdong Second Provincial General Hospital
name: Jiangmen Central Hospital
name: Shenzhen Second People's Hospital
name: First Affiliated Hospital of Guangxi Medical University
name: Dongguan People's Hospital
name: First People's Hospital of Foshan
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: Huizhou Municipal Central Hospital
name: Shenzhen Hospital of Southern Medical University
name: Affiliated Hospital of Guangdong Medical University
name: People's Hospital of Guangxi Zhuang Autonomous Region
name: First People's Hospital of Chenzhou
name: Hunan Provincial People's Hospital
name: Ganzhou City People's Hospital
name: First Affiliated Hospital of Gannan Medical University
First posted: 2025-02-06
Enrollment: 876
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with newly diagnosed AML with high risk will be divided into two cohorts, including patients being eligible for intensive chemotherapy and those with unfit status according to Ferrara 2013 criteria. In the fit cohort, patients will be randomized into accepting HVA versus IA/DA for induction with a ratio of 1:1. In the unfit cohort, patients will be randomized into accepting HVA versus VA for induction with a ratio of 1:1.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite complete remission (CRc)
timeFrame: At the end of cycle 2 (each cycle is 28 days).
Secondary outcomes:
measure: Complete remission (CR)
timeFrame: At the end of cycle 2 (each cycle is 28 days).
measure: Overall response rate (ORR)
timeFrame: At the end of cycle 2 (each cycle is 28 days).
measure: DOR
timeFrame: 1 year
measure: Rate of Measurable residual disease (MRD) negative
timeFrame: At the end of cycle 2 (each cycle is 28 days).
measure: Overall survival (OS)
timeFrame: 1 year
measure: Event-free survival (EFS)
timeFrame: 1 year
measure: Adverse events (AE)
timeFrame: The first dose until 28 days after treatment discontinuation
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Guopan Yu
role: PRINCIPAL_INVESTIGATOR
References: