azacitidine / Generic mfg. - LARVOL DELTA

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 | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P1 trial • Chronic Myelomonocytic Leukemia • Chronic Neutrophilic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Combination of LowDose Epigenetic Modifiers and TIC10 for the Activation of Antitumor Immunity and Inhibition of Tumor Growth in Gastrointestinal Cancer. (PubMed, Cancer Med) - "LD-EMs remodeled the tumor microenvironment to an immune-promoting environment. Although TIC10 could suppress cell viability and induce cell apoptosis. A combination of LD-EMs and TIC10 indicated a rational strategy through complementary mechanisms."

Journal • Gastrointestinal Cancer • Gene Therapies • Oncology • Solid Tumor • CD8 • PTPRC

Unravelling the role of epigenetic regulators during embryonic development of Rhipicephalus micropolus. (PubMed, bioRxiv) - "Inhibition of DNA methylation using 5-azacytidine (5-AZA) was associated with increased activity of the mitochondrial electron transport chain and ATP synthesis, but reduced cellular proliferation. Our findings highlight the importance of epigenetic regulation during tick embryogenesis and suggest that targeting these pathways may offer a novel and promising strategy for tick control."

Journal

Olutasidenib alone or combined with azacitidine in patients with mutant IDH1 myelodysplastic syndrome. (PubMed, Blood Adv) - P1/2 | "Olutasidenib with or without azacitidine demonstrated encouraging clinical activity and tolerability in patients with higher-risk mIDH1 MDS. NCT02719574."

Journal • Acute Myelogenous Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IDH1

5-azacytosine induces cytotoxicity via 5-methylcytosine depletion on chromatin-associated RNA in leukemia. (PubMed, bioRxiv) - "RNA-dependent effects of 5-azaC are sufficient to drive leukemia cell cytotoxicity through transcriptional repression. 5-azaC-induced caRNA m 5 C depletion impairs MBD6 binding and H2AK119ub deubiquitination. 5-azaC-induced caRNA m 5 C depletion disrupts SRSF2 chromatin-binding, impeding p300 recruitment and H3K27ac deposition. TET2 or IKZF1 depletion synergizes leukemia sensitivity to 5-azaC."

Journal • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • IKZF1 • SRSF2 • TET2

Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML. (PubMed, J Hematol Oncol) - P1 | "Although the overall efficacy was modest, this study lays the groundwork for future studies with improved patient selection and combination approaches."

Journal • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • CDK7 • RUNX1

KMHD-01: A Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients (clinicaltrials.gov) - P2 | N=114 | Completed | Sponsor: Hematology department of the 920th hospital | Recruiting ➔ Completed | Phase classification: P1/2 ➔ P2 | Trial completion date: Sep 2024 ➔ Apr 2025 | Trial primary completion date: Aug 2024 ➔ Dec 2024

Phase classification • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Epigenetic regulation of MED12: a key contributor to the leukemic chromatin landscape and transcriptional dysregulation. (PubMed, Epigenetics Chromatin) - "This study identifies a novel regulatory axis in which aberrant DNA methylation, rather than genetic mutation, drives MED12 upregulation in AML. Our findings suggest that TPRR hypermethylation may function noncanonically to support transcriptional activation, likely in cooperation with enhancer elements. These results underscore the importance of epigenetic mechanisms in AML and highlight enhancer-linked methylation as a potential contributor to oncogene dysregulation. Future studies should further explore the role of noncanonical methylation-mediated gene activation in AML pathogenesis and therapeutic targeting."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • DNMT3A • DNMT3B • MED12

CpG island demethylation and recruitment of SP1 to the promoter region regulates human thymic stromal lymphopoietin expression. (PubMed, Epigenetics) - "Demethylation of the CpG island using 5-azacytidine or siRNA-mediated knockdown of DNA methyl transferases significantly upregulated TSLP expression...Moreover, retinoic acid-induced transcription of human TSLP was associated with CpG island demethylation and SP1 binding to the TSLP promoter. These findings unravel a distinct mechanism of transcriptional regulation of the human TSLP gene and suggest possible epigenetic regulation of TSLP expression in modulating atopic and allergic disease severity in different individuals."

Journal • Allergy • TSLP

Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study. (PubMed, Ther Adv Hematol) - P2 | "We conducted a phase II trial to evaluate the efficacy and safety of azacitidine in combination with R-GDP (rituximab/gemcitabine/dexamethasone/cisplatin) in transplant-ineligible R/R DLBCL. Our study suggests that azacitidine followed by R-GDP is an effective and safe strategy for transplant-ineligible patients with R/R DLBCL. This represents the first phase II study to demonstrate the potential of epigenetic priming with azacitidine to enhance chemosensitivity in this patient population.Trial registration: ClinicalTrials.gov identifier: NCT03719989."

Journal • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • Transplantation

Long-term follow-up and combined Phase 2 results of eprenetapopt and azacitidine in patients with TP53 mutant MDS/AML. (PubMed, Hemasphere) - P1b/2 | "In this international, combined analysis of Phase 2 eprenetapopt + azacitidine patients, the combination was well-tolerated with synergistic response rates in mTP53 MDS/AML. Quality of response and NGS negativity strongly predicted OS, particularly in the setting of allo-HCT, validating NGS clearance as a critical biomarker of allo-HCT outcomes in mTP53 patients."

Journal • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Transplantation • TP53

Enasidenib as treatment for AML with IDH2 mutation: multicenter real-life study of the early-access program in Spain. (PubMed, Ann Hematol) - "Enasidenib was administered as a single agent in 18 patients, in combination with azacitidine in four patients, and with low-dose cytarabine in another one. Although enasidenib failed to demonstrate a clear overall survival advantage in phase 3 trials, the extended responses and long-term survivors observed herein underscore its therapeutic potential. Ultimately, our data support enasidenib's role as a targeted therapy for IDH2-mutated AML, indicating that expanded access to this agent is warranted to optimize outcomes in these challenging patient populations, especially for R/R AML patients."

Journal • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • IDH2

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 | Sponsor: The Methodist Hospital Research Institute

IO biomarker • Minimal residual disease • New P2 trial • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Venetoclax and azacitidine compared with intensive chemotherapy for adverse-risk acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation in first complete remission: A multicenter study of TROPHY group. (PubMed, Chin J Cancer Res) - "Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group. The TP53 mutation was independently associated with post-transplant relapse and survival. Our results suggest that IC remains the cornerstone of therapy, whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1."

Clinical • Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ASXL1 • SF3B1 • TP53

Elevated Methylation Contributes to Suppressed Expression of Special AT-Rich Sequence-Binding Protein 2 in Colorectal Cancer: A Gene-Disease Association Study. (PubMed, Health Sci Rep) - "Next, the normal colorectal FHC cell line and CRC cell lines were treated with azacytidine (AZA) to investigate whether the mRNA expression of SATB2 could be restored by demethylating agents...Additionally, the methylation state of SATB2 was correlated with tumor differentiation and metastasis. In summary, increased methylation levels contribute to decreased SATB2 expression in CRC, indicating the clinical relevance of SATB2 methylation as a potential therapeutic target for CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • SATB2

Efficacy of Azacitidine Plus Venetoclax in Acute Myeloid Leukemia Transformed from Myelodysplastic Syndrome after Failure of Azacitidine Monotherapy. (PubMed, Intern Med) - "The corresponding OR rates were 38.5%, 20.0%, and 6.7% for the AZA/VEN, chemotherapy, and mAZA groups, respectively (p=0.235). The respective median OS and EFS were 10.7 and 8.9 months for AZA/VEN, 3.2 and 2.0 months for chemotherapy, and 3.8 and 2.7 months for mAZA, and 1.7 months for BSC (OS only) (p=0.000023 for the OS and p=0.026 for the EFS), Conclusion Our findings suggest the superiority of AZA/VEN for AML patients with transformation from MDS following AZA monotherapy."

Journal • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

AMG 176 First in Human Trial in Participants With Relapsed or Refractory Multiple Myeloma and Participants With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=141 | Terminated | Sponsor: Amgen | Completed ➔ Terminated; sponsor decision, unrelated to safety

Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

VINCENT: A randomized-controlled trial evaluating venetoclax plus azacitidine versus intensive chemotherapy in patients with newly diagnosed, NPM1-mutated AML. (PubMed, Ann Hematol) - P2 | "Patients will be followed up for at least two years post enrollment. The VINCENT trial will be the first study to provide comprehensive prospective data comparing VEN/AZA to SOC, addressing both efficacy and patient-centered outcomes."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Venetoclax plus azacitidine as genetic-driven bridge-to-transplant therapy for IDH2-mutated acute myeloid leukaemia (AML) refractory to intensive chemotherapy: proof-of-concept case reports. (PubMed, Ann Hematol) - "Here, we discuss three under 60 years chemorefractory AML patients, who, given the concomitant IDH2 mutations, were started to ven/aza as bridge-to-transplant and successfully treated. These cases confirm the extraordinary sensitivity of IDH2-mutated AML to aza/ven even in the refractoriness setting and show that such less-intensive regimen can be driven by genetics offering a promising alternative to intensive salvage chemotherapy, while preserving patient fitness for allo-transplant."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • IDH2 • NPM1

Daurisoline Modulates the TBK1-Dependent Type I Interferon Pathway to Boost Anti-tumor Immunity via Targeting of LRP1. (PubMed, Research (Wash D C)) - "Mechanistically, the binding of DS to LRP1 substantially disrupted lysosomal function, which subsequently triggered 5'-azacytidine-induced protein 2-mediated TBK1 activation and IFN-I production. Furthermore, DS demonstrated synergistic effects with anti-programmed death 1 therapy and a stimulator of interferon genes agonist by remodeling the immunosuppressive microenvironment. Collectively, our findings establish LRP1 as a novel therapeutic target for cancer immunotherapy and highlight DS-driven immune reprogramming as a translatable strategy to potentiate ICB efficacy."

IO biomarker • Journal • Dyslipidemia • Oncology • CD8 • LRP1 • STING

ICP-CL-01205: ICP-248 in Combination With Azacitidine for the Treatment in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=206 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | N=102 ➔ 206

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Sequential CD19-targeted chimeric antigen receptor T cell therapy and azacitidine with venetoclax for relapsed mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report (PubMed, Zhonghua Xue Ye Xue Za Zhi) - No abstract available

Journal • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator's Choice in PTCL (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: University of Virginia | Trial completion date: Jun 2028 ➔ Jun 2030 | Trial primary completion date: Jun 2026 ➔ Jun 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Retrospective Analysis of Venetoclax Combined with Azacitidine Compared with "3+7" or Similar Regimens for Newly Diagnosed Patients with Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group."

Clinical • Journal • Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparative cardiomyocyte differentiation potential of rat adipose-derived mesenchymal stem cells from two anatomical sites: metabolomic profiling and pathway analysis. (PubMed, Front Cell Dev Biol) - "Cardiomyocyte differentiation was induced using 5-azacytidine, and morphological changes were assessed via phase-contrast microscopy and immunofluorescence staining for cardiac troponin T (cTnT)...The anatomical origin of AD-MSCs influences their metabolic landscape during cardiomyocyte differentiation. Peri-ovarian AD-MSCs demonstrated greater metabolic adaptability, potentially favoring their differentiation capacity, making them a promising candidate for cardiac regenerative applications."

Journal • Preclinical • Metabolic Disorders • CD44 • ITGB1 • THY1