Efficacy of Hypomethylating Agents vs. Intensive Chemotherapy in Acute Myeloid Leukemia Using 5hmC as a Blood-Based Minimal Residual Disease Marker

Summary

This is a therapeutic intervention trial evaluating the clinical utility of a novel blood-based epigenetic biomarker-genome-wide 5-hydroxymethylcytosine (5hmC) in cell-free DNA (cfDNA)-for assessing measurable residual disease (MRD) in patients with newly diagnosed acute myeloid leukemia (AML). The study compares the efficacy of hypomethylating agent (HMA)-based therapy versus intensive induction chemotherapy, using the 5hmC biomarker to guide post-induction treatment decisions. Approximately 112 adult patients will be enrolled and assigned to treatment arms based on a stratified sampling scheme. Blood samples will be collected at defined intervals to assess MRD status. Primary endpoints include minimal residual disease (MRD) negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS).

Timeline

Start

2026-04

Primary completion

2028-12

Completion

2029-12

Publications

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• Background Shao J, Olsen RJ, Kasparian S, He C, Bernicker EH, Li Z. Cell-Free DNA 5-Hydroxymethylcytosine Signatures for Lung Cancer Prognosis. Cells. 2024 Feb 6;13(4):298. doi: 10.3390/cells13040298.
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• Background Chiu BC, Zhang Z, You Q, Zeng C, Stepniak E, Bracci PM, Yu K, Venkataraman G, Smith SM, He C, Zhang W. Prognostic implications of 5-hydroxymethylcytosines from circulating cell-free DNA in diffuse large B-cell lymphoma. Blood Adv. 2019 Oct 8;3(19):2790-2799. doi: 10.1182/bloodadvances.2019000175.
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• Background Han D, Lu X, Shih AH, Nie J, You Q, Xu MM, Melnick AM, Levine RL, He C. A Highly Sensitive and Robust Method for Genome-wide 5hmC Profiling of Rare Cell Populations. Mol Cell. 2016 Aug 18;63(4):711-719. doi: 10.1016/j.molcel.2016.06.028. Epub 2016 Jul 28.
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Indications