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. 2025 Mar 3;2(3):100085.
doi: 10.1016/j.bneo.2025.100085. eCollection 2025 Aug.

Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm

Suravi Raychaudhuri  1 , Ted A Gooley  2 , Allegra Rasmussen  1 , Kim Quach  1 , Eva Gill  1 , Anna B Halpern  1   2 , Jacob S Appelbaum  1   2 , Cristina M Ghiuzeli  1   2 , Paul C Hendrie  1   2 , Ryan D Cassaday  1   2 , Roland B Walter  1   3   4 , Mary-Elizabeth M Percival  1   2
Affiliations

Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm

Suravi Raychaudhuri et al. Blood Neoplasia. .

Abstract

Intensifying induction by combining venetoclax with a high-dose cytarabine regimen may improve outcomes for high-risk populations such as adult patients with adverse-risk newly diagnosed or relapsed acute myeloid leukemia. In a phase 1 trial testing the novel combination of venetoclax and CLAG-M (cladribine, high-dose cytarabine, granulocyte colony-stimulating factor [G-CSF], and mitoxantrone), the maximum tolerated dose was venetoclax 400 mg on days 1 through 14, combined with cladribine 5 mg/m2 on days 1 through 5, cytarabine 1.5 g/m2 on days 1 through 5, G-CSF 5 μg/kg on days 0 through 5, and mitoxantrone 16 or 18 mg/m2 on days 1 through 3 (for relapsed/refractory and newly diagnosed adverse-risk patients, respectively). The 28-day mortality rate was 5%. Composite complete remission (CR) rate (CR + CR with incomplete hematologic recovery) was 65%. These findings support further phase 2 study of venetoclax in combination with CLAG-M. This trial was registered at www.ClinicalTrials.gov as #NCT04797767.

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Conflict of interest statement

Conflict-of-interest disclosure: A.B.H. provided consultancy for Karyopharm Therapeutics; and received research funding from Imago Biosciences, Merck, Bayer Pharmaceuticals, Gilead Sciences, Jazz Pharmaceuticals, Incyte, Karyopharm Therapeutics, Disc Medicine, Protagonist, PharmEssentia, and Sumitomo. J.S.A. received honoraria from Incyte. R.B.W. did consultancy for Wugen, Inc; and received research funding from Aptevo, Celgene/Bristol Myers Squibb (BMS), ImmunoGen, Janssen, Jazz, Kite, Kura, Pfizer, and Vor Biopharma. R.D.C. received research funding from Amgen, Kite/Gilead, Incyte, Merck, Pfizer, Servier, and Vanda Pharmaceuticals; provided consultancy for/received honoraria from Autolus, Amgen, Jazz, Kite/Gilead, and Pfizer; reports membership on a board or advisory committee for Autolus and PeproMene Bio; and reports that a spouse was employed by and owned stock in Seagen. M.-E.M.P. received research funding from AbbVie, Ascentage, Astex, Biosight, BMS/Celgene, Glycomimetics, Immunogen, Nohla Therapeutics, Oscotec, Pfizer, Telios, and VinceRx. The remaining authors declare no competing financial interests.

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References

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    1. Halpern AB, Othus M, Huebner EM, et al. Phase I/II trial of cladribine, high-dose cytarabine, mitoxantrone, and G-CSF with dose-escalated mitoxantrone for relapsed/refractory acute myeloid leukemia and other high-grade myeloid neoplasms. Haematologica. 2019;104(4):e143–e146. - PMC - PubMed
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