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    DRUG CLASS:

    Hypomethylating agent

    Related drugs:
    24d
    NCI-2018-01812: Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (clinicaltrials.gov)
    P2, N=50, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027
    Trial completion date • Trial primary completion date
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    CD33 (CD33 Molecule)
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    CD33 positive
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    Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    1m
    Cladribine Venetoclax in Monocytic AML (clinicaltrials.gov)
    P2, N=20, Recruiting, University of Colorado, Denver | N=40 --> 20
    Enrollment change
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    Venclexta (venetoclax)
    3ms
    NCI-2018-01812: Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (clinicaltrials.gov)
    P2, N=50, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    CD33 (CD33 Molecule)
    |
    CD33 positive
    |
    Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    3ms
    Pacritinib With Standard of Care Azacitidine or Decitabine as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant for Patients With Accelerated and Blast Phase Myeloproliferative Neoplasms (clinicaltrials.gov)
    P2, N=27, Not yet recruiting, University of Washington
    New P2 trial
    |
    azacitidine • Inqovi (decitabine/cedazuridine) • Vonjo (pacritinib)
    3ms
    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 | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    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)
    |
    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
    4ms
    STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov)
    P2, N=39, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.
    Trial termination
    |
    azacitidine • decitabine • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
    5ms
    M-HArbOr: Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    New P1 trial
    |
    azacitidine • decitabine • Ojjaara (momelotinib)
    5ms
    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
    New P2 trial • IO biomarker • Minimal residual disease
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • decitabine
    5ms
    GIMEMA 2320: Prospective and Retrospective Observational Evaluation of Real World Outcome of Unfit AML Patients Treated With the Combination Venetoclax Plus Hypomethylating Agents, Under the Italian Law No.648/96 (clinicaltrials.gov)
    P=N/A, N=202, Completed, Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting --> Completed | N=104 --> 202 | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2022 --> Sep 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Real-world evidence
    |
    Venclexta (venetoclax)
    6ms
    Effect of the IDH1 inhibitor combined with hypomethylating agents on acute myeloid leukemia. (PubMed, Tumori)
    The IDH1 inhibitor with HMAs suppressed IDH1R132H-MOLM-13 cell proliferation and viability and decreased the methylation level by repressing the phosphorylation of the PI3K/AKT pathway, showing a synergistic inhibitory effect.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • DNMT1 (DNA methyltransferase 1)
    |
    IDH1 mutation • IDH1 R132
    |
    azacitidine • decitabine • Tibsovo (ivosidenib)
    6ms
    Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML. (PubMed, J Clin Oncol)
    Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, IC-ineligible IDH-mutant AML, further prospective studies comparing IDH-triplet versus IDH-doublet regimens are warranted.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 mutation • IDH2 mutation
    |
    Venclexta (venetoclax) • azacitidine • decitabine • Tibsovo (ivosidenib) • Idhifa (enasidenib)
    6ms
    Acquired Resistance to Decitabine Associated with the Deoxycytidine Kinase A180P Mutation: Implications for the Order of Hypomethylating Agents in Myeloid Malignancies Treatment. (PubMed, Int J Mol Sci)
    The backbone of therapy for elderly patients with myelodysplastic syndromes and acute myeloid leukemia consists of hypomethylating agents 5-aza-2'-deoxycytidine (DAC) and 5-azacytidine (AZA). This highlights the importance of also evaluating DCK at the protein and/or enzymatic activity levels in patients. The loss of functional DCK impairs the phosphorylation of deoxynucleosides, conferring resistance to DAC, gemcitabine, and cytarabine, but AZA, phosphorylated by uridine-cytidine kinase, remains effective and may represent a therapeutic alternative for patients with acquired DAC resistance.
    Preclinical • Journal
    |
    DCK (Deoxycytidine Kinase 2)
    |
    gemcitabine • cytarabine • azacitidine • decitabine