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

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.

Timeline

Start

2026-03-31

Primary completion

2028-03-31

Completion

2029-03-31

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

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