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

NCT07507825 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026IIT031-1
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Acute myeloid leukemia (AML); Venetoclax; Homoharringtonine; Azacitidine; Elderly/unfit patients

Outcome Measures

Primary Outcomes (1)

• CRc（CR+CRi）

  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 Outcomes (5)

• ORR（CR+CRi+MLFS+PR）

  After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

• OS

  1year

• RFS

  1year

• MRD

  After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

• NCICTCAEv5.0

  After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Other Outcomes (1)

• EBS

  After 2 cycles of induction therapy(each cycle is 28 days; approximately Day 56)

Study Arms (1)

VHAG Regimen Treatment Arm

EXPERIMENTAL

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; Drug: Intervention for Homoharringtonine; Drug: Intervention for Azacitidine; Drug: Intervention for G-CSF

Interventions

Intervention for Venetoclax DRUG

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.

VHAG Regimen Treatment Arm

Intervention for Homoharringtonine DRUG

Intravenous infusion of homoharringtonine at a dose of 1 mg/m² daily from Day 1 to Day 7 of each induction cycle.

VHAG Regimen Treatment Arm

Intervention for Azacitidine DRUG

Subcutaneous or intravenous administration of azacitidine at a dose of 75 mg/m² daily from Day 1 to Day 7 of each induction cycle.

VHAG Regimen Treatment Arm

Intervention for G-CSF DRUG

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.

VHAG Regimen Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University

Hangzhou, Zhejiang, 310006, China

Location

Related Publications (14)

• Yin Z, Gao Y, Bu X, Wang J, Yao Z, Liu Q, Zhang Y, Yu G, Ping B. Homoharringtonine sensitized resistant acute myeloid leukemia cells to venetoclax-induced apoptosis. Leuk Lymphoma. 2024 Dec;65(14):2138-2150. doi: 10.1080/10428194.2024.2400228. Epub 2024 Sep 5.

  PMID: 39235111 BACKGROUND

• Yu G, Zhang Y, Yu S, Yin Z, Weng G, Xu N, Du X, Lin D, Xiao J, Sun Z, Zhang H, Liang X, Guo Z, Zhao W, Dai M, Fan Z, Xuan L, Liu H, Xu D, Ye J, Jiang X, Shi P, Jin H, Liu Q. Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study. Clin Cancer Res. 2025 Jan 6;31(1):87-97. doi: 10.1158/1078-0432.CCR-24-1332.

  PMID: 39531539 BACKGROUND

• DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Dohner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hajek R, Porkka K, Illes A, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.

  PMID: 32786187 BACKGROUND

• Um HD. Bcl-2 family proteins as regulators of cancer cell invasion and metastasis: a review focusing on mitochondrial respiration and reactive oxygen species. Oncotarget. 2016 Feb 2;7(5):5193-203. doi: 10.18632/oncotarget.6405.

  PMID: 26621844 BACKGROUND

• Choi JH, Bogenberger JM, Tibes R. Targeting Apoptosis in Acute Myeloid Leukemia: Current Status and Future Directions of BCL-2 Inhibition with Venetoclax and Beyond. Target Oncol. 2020 Apr;15(2):147-162. doi: 10.1007/s11523-020-00711-3.

  PMID: 32319019 BACKGROUND

• Dombret H, Raffoux E, Gardin C. Acute myeloid leukemia in the elderly. Semin Oncol. 2008 Aug;35(4):430-8. doi: 10.1053/j.seminoncol.2008.04.013.

  PMID: 18692693 BACKGROUND

• Pollyea DA, Kohrt HE, Medeiros BC. Acute myeloid leukaemia in the elderly: a review. Br J Haematol. 2011 Mar;152(5):524-42. doi: 10.1111/j.1365-2141.2010.08470.x.

  PMID: 21314823 BACKGROUND

• Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysak D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. doi: 10.1200/JCO.2011.38.9429. Epub 2012 Jun 11.

  PMID: 22689805 BACKGROUND

• Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.

  PMID: 25987659 BACKGROUND

• Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, Tidefelt U, Wahlin A, Hoglund M. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009 Apr 30;113(18):4179-87. doi: 10.1182/blood-2008-07-172007. Epub 2008 Nov 13.

  PMID: 19008455 BACKGROUND

• SEER Cancer Stat Facts: Acute Myeloid Leukemia. 2017 2025-12-18]; Available from: https://seer.cancer.gov/statfacts/html/amyl.html.

  BACKGROUND

• Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.

  PMID: 28055103 BACKGROUND

• Wang H, Wang X, Shi T, Wei S, Li X, Leng Y, Wu Y, Sun M, He P, Zhu HH. Granulocyte colony-stimulating factor plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia: a multicenter phase 2 trial. Blood Cancer J. 2025 Oct 27;15(1):184. doi: 10.1038/s41408-025-01389-4. No abstract available.

  PMID: 41145434 BACKGROUND

• Yin Z, Yao Z, Chen D, Zhang Y, Weng G, Du X, Lin D, Xiao J, Sun Z, Zhang H, Liang X, Guo Z, Zhao W, Xuan L, Jiang X, Shi P, Liu Q, Ping B, Yu G. Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia. J Cancer Res Clin Oncol. 2024 Jul 6;150(7):336. doi: 10.1007/s00432-024-05861-9.

  PMID: 38969948 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Methods; venetoclax; Homoharringtonine; Azacitidine; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Investigative Techniques; Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Xiangmin Tong, DR

CONTACT

86-13750816623; tongxiangmin@163.com

Peipei Ye, DR

CONTACT

86-13685832706; 39612903@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open-label, non-randomized, interventional study. All enrolled subjects will receive the same study regimen consisting of venetoclax, homoharringtonine, azacitidine, and G-CSF (VHAG) according to the protocol-specified schedule. No control or comparator group is included. The intervention model is designed to evaluate the safety and efficacy of the VHAG combination regimen in the target population of newly diagnosed acute myeloid leukemia patients who are elderly or unfit for standard intensive chemotherapy.

Study Record Dates

• First Submitted: March 22, 2026
• First Posted: April 2, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)