Exploratory Study of Venetoclax, Homoharringtonine, Azacitidine Plus G-CSF for Newly Diagnosed AML (VHAG) (VHAG)

March 30, 2026 updated by: First People's Hospital of Hangzhou

A Prospective, Multicenter, Exploratory Study of Venetoclax, Homoharringtonine, and Azacitidine Combined With G-CSF in Elderly or Unfit Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is a single-arm, prospective, multi-center exploratory clinical trial. A total of 61 patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable for intensive chemotherapy will be enrolled. The Simon two-stage design will be adopted to control the type I and type II errors, with the minimum acceptable composite remission rate of 65% and a power of 80%.

Prior to treatment, subjects will undergo screening within 28 days, including bone marrow aspiration, genetic testing, ECOG performance status assessment, and organ function evaluation. Data will be recorded in Excel and subject to unified quality control. During the treatment period, G-CSF (granulocyte colony-stimulating factor) will be administered subcutaneously as appropriate, and supportive care such as antiemetic and hydration therapy will be provided routinely.

For patients who achieve remission, individualized consolidation therapy will be given: those eligible for transplantation will undergo allogeneic hematopoietic stem cell transplantation; those who can tolerate moderate-intensity treatment will receive consolidation with medium-dose cytarabine first, followed by 4 cycles of VHAG regimen consolidation. Patients with FLT3 mutations will receive additional targeted therapy during consolidation.

Safety assessment will be conducted in accordance with the NCI-CTCAE Version 5.0. For grade 4 hematological toxicity or severe non-hematological toxicity, the treatment dose will be adjusted or the treatment will be suspended. Severe adverse events will be reported in a timely manner, and all research-related data will be retained for at least 10 years in accordance with relevant regulations.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

According to the detailed inclusion and exclusion criteria, first-line induction therapy: VHAG regimen Venetoclax 100 mg on day 2, 200 mg on day 3, 400 mg on days 4-10; Homoharringtonine 1 mg/m² on days 1-7; Azacitidine 75 mg/m² on days 1-7; G-CSF 5 μg/kg subcutaneously starting on day 0;G-CSF to be discontinued if WBC ≥ 30 × 10⁹/L.

One cycle every 4 weeks, for a total of 2 cycles.Patients who achieve CR/CRi/MLFS/PR after the first cycle will receive one additional cycle of the same regimen for consolidation(venetoclax 400 mg on days 1-7 in the second course).

Subsequent treatment After achieving remission, re-evaluate tolerability comprehensively based on age, performance status, comorbidities, and other factors.

Patients eligible for transplantation will undergo allogeneic hematopoietic stem cell transplantation.

Transplant-ineligible patients:

Those tolerable to intensive chemotherapy may receive1-2 courses of intermediate-dose cytarabine consolidation,followed by 4 courses of VHAG consolidation.

Those intolerant to intensive chemotherapy will continue6 courses of VHAG consolidation.

Patients with FLT3 mutations in the intermediate- or high-risk groups may receive combination therapy with a FLT3 inhibitor during consolidation.

Endpoints Primary endpoint: Composite complete remission rate (CRc: CR + CRi)

Secondary endpoints:

Overall response rate (ORR: CR + CRi + MLFS + PR) Overall survival (OS) Relapse-free survival (RFS) Rate of measurable residual disease (MRD) negativity Safety Hematologic and non-hematologic toxicities (NCI CTCAE version 5.0) Exploratory biomarker evaluation

Study Type

Interventional

Enrollment (Estimated)

61

Phase

  • Phase 2

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

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310006
        • Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University
        • Contact:
        • Principal Investigator:
          • Xiangmin Tong, Dr
        • Sub-Investigator:
          • Yaping Xie, Dr
        • Sub-Investigator:
          • Peipei Ye, Dr
        • Sub-Investigator:
          • Ying Lu, Dr
        • Sub-Investigator:
          • Jie Jin, Dr
        • Sub-Investigator:
          • Hongyan Tong, Dr
        • Sub-Investigator:
          • Junyu Zhang, Dr
        • Sub-Investigator:
          • Weiying Feng, Dr
        • Sub-Investigator:
          • Qunyi Guo, Dr
        • Sub-Investigator:
          • Jingcheng Zhang, Dr
        • Sub-Investigator:
          • Li Huang, Dr
        • Sub-Investigator:
          • Weiguo Zhu, Dr
        • Sub-Investigator:
          • Huifang Jiang, Dr
        • Sub-Investigator:
          • Gongqiang Wu, Dr
        • Sub-Investigator:
          • Sai Chen, Dr
        • Sub-Investigator:
          • Ying Lin, Dr
        • Sub-Investigator:
          • Lihong Shou, Dr
        • Sub-Investigator:
          • Jing Le, Dr
        • Sub-Investigator:
          • Hui Zeng, Dr
        • Sub-Investigator:
          • Yongmin Xia, Dr
        • Principal Investigator:
          • Beili Hu, Dr

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:

  • The patient has fully understood the study, voluntarily participated, and signed the informed consent form (ICF).
  • Newly diagnosed acute myeloid leukemia (AML) confirmed by bone marrow morphology, immunophenotyping, cytogenetics, and/or molecular biology testing, in accordance with the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2022 edition).
  • No prior systemic therapy for AML (including induction, consolidation, or maintenance therapy).
  • Patients judged unfit for standard cytarabine plus anthracycline induction chemotherapy due to age or comorbidities.
  • Short-term use of hydroxyurea or low-dose cytarabine before enrollment to control hyperleukocytosis is permitted.
  • Age ≥ 75 years, or age 18-74 years with any of the following comorbidities:
  • ECOG performance status 2-3
  • History of congestive heart failure, left ventricular ejection fraction (LVEF) ≤ 50%, or chronic stable angina
  • Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% predicted, or forced expiratory volume in 1 second (FEV1) ≤ 65% predicted
  • Creatinine clearance 30-45 mL/min (≥ 30 and < 45)
  • Moderate hepatic impairment: total bilirubin > 1.5 × ULN and ≤ 3 × ULN
  • Other comorbidities deemed unfit for standard chemotherapy by the investigator
  • Estimated survival time ≥ 12 weeks.
  • For patients aged ≥ 75 years: ECOG performance status 0-2.
  • For patients aged 18-74 years: ECOG performance status 0-3.
  • Creatinine clearance ≥ 30 mL/min (calculated by the Cockcroft-Gault formula).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 × ULN; may be relaxed to ≤ 3 × ULN in patients with leukemic hepatic infiltration.
  • For patients < 75 years old, total bilirubin ≤ 3 × ULN.

Exclusion Criteria:

  • Acute promyelocytic leukemia (APL).
  • History of prior myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, myelofibrosis, etc.
  • Prior receipt of hypomethylating agents, venetoclax (VEN), or systemic chemotherapy for myelodysplastic syndromes (MDS).
  • Prior receipt of any investigational drug or device therapy for MDS/AML.
  • Concurrent participation in another clinical trial.
  • AML with central nervous system (CNS) involvement confirmed by imaging or cerebrospinal fluid examination.
  • Positive HIV antibody during the screening period.
  • Positive HBsAg or HCV antibody with a high-sensitivity viral load above the lower limit of detection within 3 months (excluding those who are cured or with persistent low-level replication).
  • Ingestion of grapefruit, grapefruit juice, Seville oranges, star fruit, or their products within 72 hours prior to the first dose.
  • Chronic respiratory failure requiring long-term oxygen therapy.
  • Presence of severe cardiac, hepatic, renal, endocrine, metabolic, immune, neurological, or psychiatric disorders.
  • History of hypersensitivity to the study drug (including azacitidine excipients).
  • Impaired drug absorption due to malabsorption syndrome, short bowel syndrome, or other conditions affecting oral drug absorption.
  • Active tuberculosis or other severe infections requiring intravenous anti-infective therapy for ≥7 days.
  • Presence of a second malignancy within 2 years prior to enrollment, excluding cured carcinoma in situ of the cervix or breast, completely resected basal cell carcinoma or localized squamous cell carcinoma of the skin, or localized malignancies cured by surgery and requiring no further follow-up.
  • The investigator judges that the patient is otherwise ineligible to participate in this study.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VHAG Regimen Treatment Arm
All enrolled patients will receive the VHAG combination regimen, consisting of venetoclax, homoharringtonine, azacitidine, and G-CSF, according to the study protocol. The regimen includes induction therapy followed by optional consolidation cycles as specified in the protocol.
Drug: Intervention for Venetoclax
Oral administration of venetoclax. The starting dose is 100 mg on Day 2, 200 mg on Day 3, and 400 mg once daily from Day 4 to Day 10 of each induction cycle. Dose adjustments may be made per protocol based on tolerability and safety.
Drug: Intervention for Homoharringtonine
Intravenous infusion of homoharringtonine at a dose of 1 mg/m² daily from Day 1 to Day 7 of each induction cycle.
Drug: Intervention for Azacitidine
Subcutaneous or intravenous administration of azacitidine at a dose of 75 mg/m² daily from Day 1 to Day 7 of each induction cycle.
Drug: Intervention for G-CSF
Subcutaneous administration of G-CSF at a dose of 5 μg/kg daily, initiated prior to the start of induction therapy (Day 0). Discontinuation will be per protocol when the white blood cell count (WBC) exceeds 30 × 10⁹/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CRc（CR+CRi）
Time Frame: After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
Composite complete remission (CR) plus CR with incomplete hematologic recovery
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR（CR+CRi+MLFS+PR）
Time Frame: After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
Objective Response Rate (Complete Response + Complete Response with incomplete hematologic recovery + Marrow Leukemia-Free State + Partial Response)
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
OS
Time Frame: 1year
Overall Survival
1year
RFS
Time Frame: 1year
Relapse-Free Survival
1year
MRD
Time Frame: After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
Rate of negative conversion of evaluable minimal residual disease (MRD)
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
NCICTCAEv5.0
Time Frame: After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
EBS
Time Frame: After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)
Exploratory biomarker assessment
After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Collaborators and Investigators

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

Sponsor

First People's Hospital of Hangzhou

Collaborators

Ningbo Medical Center Lihuili Hospital
Jinhua People's Hospital
Second Affiliated Hospital of Wenzhou Medical University
Zhejiang University
The Central Hospital of Lishui City
Shaoxing People's Hospital
Shaoxing Second Hospital
Jinhua Central Hospital
Taizhou Hospital
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
The Second Affiliated Hospital of Jiaxing University
The Affiliated People's Hospital of Ningbo University
Zhejiang Provincial Tongde Hospital
Dongyang People's Hospital
Affiliated Hospital of Jiaxing University
Yuyao People's Hospital
Huzhou Central Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

March 31, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

March 22, 2026

First Submitted That Met QC Criteria

March 30, 2026

First Posted (Actual)

April 2, 2026

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026IIT031-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The individual participant data (IPD) will not be shared, due to the constraints of patient privacy protection, informed consent limitations, and institutional data management policies. All data generated from this study will be used solely for the primary research objectives of this trial, and will not be disclosed to external third-party researchers without additional ethical approval and explicit patient consent.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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