Trial reportClinical epigenetics2019
Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia.
Trial report in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01261312 (A Phase 1-2, Dose Escalation, Multicenter Study of Two Subcutaneous Regimens of SGI-110, a DNA Hypomethylating Agent, in Subjects With Intermediate or High-Risk Myelodysplastic Syndromes), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1-2, Dose Escalation, Multicenter Study of Two Subcutaneous Regimens of SGI-110, a DNA Hypomethylating Agent, in Subjects With Intermediate or High-Risk Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML)
Who cites it
19 citing papers in PubMed.
- A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML.Blood neoplasia · 2025Trial
- Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial.Blood advances · 2024Trial
- Targeting nucleotide metabolism and epigenetic regulation to overcome the differentiation blockade in AML.Leukemia research reports · 2026Review
- Transcriptomic analysis of non-leukemic cell subsets in azacytidine-responsive AML highlights pathways associated with adhesion, platelet aggregation, and angiogenesis in mice and humans.Molecular medicine (Cambridge, Mass.) · 2025Article
- FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia.Current medicinal chemistry · 2025Article
- Effects of Hypomethylating Agents on Gene Modulation in the Leukemic Microenvironment and Disease Trajectory in a Mouse Model of AML.bioRxiv : the preprint server for biology · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Article
- An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment.International journal of molecular sciences · 2023Review
- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
- Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy.Journal of experimental & clinical cancer research : CR · 2022Article
- Emerging role of different DNA methyltransferases in the pathogenesis of cancer.Frontiers in pharmacology · 2022Review
- DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application.Clinical epigenetics · 2021Review
- The Roles of DNA Demethylases in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.Journal of biomedical science · 2021Review
- Following in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes?Leukemia & lymphoma · 2020Review
- DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy.Cancers · 2020Review
- Clinical implications of recurrent gene mutations in acute myeloid leukemia.Experimental hematology & oncology · 2020Review
- Identification of TwoJournal of oncology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundGuadecitabine is a novel DNA methyltransferase (DNMT) inhibitor with improved pharmacokinetics and clinical activity in a subset of patients with relapsed/refractory acute myeloid leukemia (r/r AML), but identification of this subset remains difficult.
methodsTo search for biomarkers of response, we measured genome-wide DNA methylation, mutations of 54 genes, and expression of a panel of 7 genes in pre-treatment samples from 128 patients treated at therapeutic doses in a phase I/II study.
resultsResponse rate to guadecitabine was 17% (2 complete remission (CR), 3 CR with incomplete blood count recovery (CRi), or CR with incomplete platelets recovery (CRp)) in the phase I component and 23% (14 CR, 9 CRi/CRp) in phase II. There were no strong mutation or methylation predictors of response. Gene expression clustering defined a subset of patients (~ 20%) that had (i) high DNMT3B and low CDKN2B, CTCF, and CDA expression; (ii) enrichment for KRAS/NRAS mutations; (iii) frequent CpG island hypermethylation; (iv) low long interspersed nuclear element 1 (LINE-1) hypomethylation after treatment; and (v) resistance to guadecitabine in both phase I (response rate 0% vs. 33%, p = 0.07) and phase II components of the study (response rate 5% vs. 30%, p = 0.02). Multivariate analysis identified peripheral blood (PB) blasts and hemoglobin as predictors of response and cytogenetics, gene expression, RAS mutations, and hemoglobin as predictors of survival.
conclusionsA subset of patients (~ 20%) with r/r AML is unlikely to benefit from guadecitabine as a single agent. In the remaining 80%, guadecitabine is a viable option with a median survival of 8 months and a 2-year survival rate of 21%.
trial registrationNCT01261312 .
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.