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

February 4, 2025 updated by: Nanfang Hospital, Southern Medical University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

876

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Guopan Yu
  • Phone Number: +8615876559968
  • Email: yugpp@163.com

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Department of Hematology,Nanfang Hospital, Southern Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IC regiment for Fit-AML
Drug: Standard Chemotherapy
Standard Chemotherapy includes IA(Idarubicin combined with Cytarabine) or DA(Daunorubicin combined with Cytarabine). IDA is given by venous drip daily at 12mg/m2, or DNR is given by venous drip daily at 60mg/m2, from day 1-3, combined with Ara-C at 100mg/m2 by continuously venous drip from day 1-7.
Experimental: HVA regiment for Fit-AML
Drug: HVA
Homoharringtonine (HHT) is given by venous drip daily at 1 mg/m2 from day 1 to 7. Venetoclax (VEN) is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 14. Azacitidine (AZA) is given 75 mg/m2 subcutaneously from day 1 to 7.
Active Comparator: VA regiment for unfit-AML
Drug: VA
VEN is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 28, and AZA (75 mg/m2) is given subcutaneously from day 1 to 7.
Experimental: HVA regiment for unfit-AML
Drug: HVA
Homoharringtonine (HHT) is given by venous drip daily at 1 mg/m2 from day 1 to 7. Venetoclax (VEN) is given 100 mg on day 1, 200 mg on day 2, and 400 mg orally from day 3 to day 14. Azacitidine (AZA) is given 75 mg/m2 subcutaneously from day 1 to 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite complete remission (CRc)
Time Frame: 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).
At the end of cycle 2 (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DOR
Time Frame: 1 year
duration of response
1 year
Complete remission (CR)
Time Frame: 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.
At the end of cycle 2 (each cycle is 28 days).
Overall response rate (ORR)
Time Frame: At the end of cycle 2 (each cycle is 28 days).
ORR includes CRc, partial response (PR), and morphologic leukemia-free state (MLFS).
At the end of cycle 2 (each cycle is 28 days).
Rate of Measurable residual disease (MRD) negative
Time Frame: 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%.
At the end of cycle 2 (each cycle is 28 days).
Overall survival (OS)
Time Frame: 1 year
OS is calculated from enrollment to death or the last follow-up.
1 year
Event-free survival (EFS)
Time Frame: 1 year
EFS is calculated from enrollment to the date of relapse or death or the last follow-up.
1 year
Adverse events (AE)
Time Frame: 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.
The first dose until 28 days after treatment discontinuation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital, Southern Medical University

Collaborators

Guangdong Provincial Hospital of Traditional Chinese Medicine
Guangzhou First People's Hospital
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Hunan Provincial People's Hospital
First People's Hospital of Chenzhou
First People's Hospital of Foshan
Shenzhen Second People's Hospital
Dongguan People's Hospital
Huizhou Municipal Central Hospital
Guangdong Second Provincial General Hospital
People's Hospital of Guangxi
Jiangmen Central Hospital
First Affiliated Hospital of Guangxi Medical University
Shenzhen Hospital of Southern Medical University
First Affiliated Hospital of Gannan Medical University
Ganzhou City People's Hospital
Affiliated Hospital of Guangdong Medical University

Investigators

  • Principal Investigator: Guopan Yu, Nanfang Hospital, Southern Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

January 16, 2025

First Submitted That Met QC Criteria

February 4, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 4, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NFEC-2024-576

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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