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DRUG CLASS:

Hypomethylating agent

19d
Initial leukemic epigenomic state determines hypomethylating agent response. (PubMed, Nat Commun)
Hypomethylation and chromatin accessibility at ZNF143- and CTCF-binding sites results in activation of HOXB4, which defines the HSC/MPP-like state and HMA-sensitivity. Our study provides evidence that the epigenomic state of the LSC is a major determinant of response to HMAs, and demonstrates that a routine clinical assay can identify patients who will respond.
Journal
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HOXB4 (Homeobox B4) • ZNF143 (Zinc Finger Protein 143)
19d
NCI-2022-02215: A Phase II Study of Vibecotamab (XmAb14045) for MRD- Positive AML and MDS After Hypomethylating Agent Failure (clinicaltrials.gov)
P2, N=51, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2026 --> May 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2026 --> May 2026; <75% participation
Trial completion date • Trial termination • Trial primary completion date • Minimal residual disease
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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vibecotamab (XmAb14045)
21d
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)
P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Trial completion date: Mar 2027 --> Mar 2030
Trial completion date
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)
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Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan
22d
Enrollment change • Trial withdrawal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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IDH1 mutation
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azacitidine • Rezlidhia (olutasidenib)
23d
22P.205: Navitoclax in Relapsed or Refractory High-Risk Myelodysplastic Syndrome (clinicaltrials.gov)
P1, N=6, Completed, Thomas Jefferson University | Active, not recruiting --> Completed
Trial completion
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BCL2 (B-cell CLL/lymphoma 2)
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Venclexta (venetoclax) • azacitidine • decitabine • navitoclax (ABT 263)
2ms
TAGALONG: Tagraxofusp and Azacitidine With Venetoclax in Newly Diagnosed Secondary AML After Hypomethylating Agents (clinicaltrials.gov)
P2, N=53, Recruiting, Joshua Zeidner | Trial completion date: Dec 2027 --> Jul 2031 | Trial primary completion date: Aug 2027 --> Jul 2030
Trial completion date • Trial primary completion date
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
2ms
Iadademstat With Hypomethylating Agent in Patients With Myelodysplastic Syndrome (clinicaltrials.gov)
P1, N=12, Recruiting, Medical College of Wisconsin | Trial completion date: Oct 2027 --> Dec 2027 | Trial primary completion date: Oct 2026 --> Dec 2026
Trial completion date • Trial primary completion date
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iadademstat (ORY-1001)
3ms
Enrollment open
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azacitidine • Ojjaara (momelotinib)
3ms
Maintenance Therapy of Hypomethylating Agent (HMA) in Favorable Risk Acute Myeloid Leukemia (AML) Patients (clinicaltrials.gov)
P2, N=77, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Dec 2025 --> Dec 2026
Trial primary completion date
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NPM1 (Nucleophosmin 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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NPM1 mutation
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azacitidine • decitabine
3ms
Efficacy of Hypomethylating Agents vs. Intensive Chemotherapy in Acute Myeloid Leukemia Using 5hmC as a Blood-Based Minimal Residual Disease Marker (clinicaltrials.gov)
P2, N=112, Not yet recruiting, The Methodist Hospital Research Institute | Initiation date: Jul 2025 --> Apr 2026
Trial initiation date • IO biomarker • Minimal residual disease
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Venclexta (venetoclax) • cytarabine • azacitidine • decitabine
3ms
Venetoclax Plus Hypomethylating Agents and Subcutaneous Cytarabine for CEBPA-Mutated AML (clinicaltrials.gov)
P1/2, N=29, Recruiting, The First Affiliated Hospital of Soochow University
New P1/2 trial
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CEBPA (CCAAT Enhancer Binding Protein Alpha)
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Venclexta (venetoclax) • cytarabine • azacitidine
3ms
Discontinuation of Hypomethylating Agent and Venetoclax in Patients With AML MRD (clinicaltrials.gov)
P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Aug 2026 --> Oct 2027
Trial primary completion date
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Venclexta (venetoclax) • azacitidine • decitabine