azacitidine

P2, N=60, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1/2, N=240, Recruiting, Aptose Biosciences Inc. | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Nov 2026

Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Median duration of CRc and ORR: 13.15 (range: 2.4-48.7) and 14.3 months (range: 2.4-48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70-23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post-MPN mIDH1 AML.

We have found miR-198 to be upregulated in OSCC cells treated with 5-Azacytidine, a known DNA methyltransferase inhibitor...Delivery of a synthetic miR-198 mimic to OSCC cells results in a significant decrease in xenograft size in nude mice, potentiating its use in therapeutics. These results suggest that miR-198 is epigenetically silenced in OSCC, which promotes tumor growth, in part, by upregulating the levels of TOPORS.

P3, N=465, Active, not recruiting, AbbVie | Trial completion date: Nov 2026 --> Jan 2028 | Trial primary completion date: Nov 2026 --> Jan 2028

P2, N=20, Recruiting, Beijing 302 Hospital

The most well-studied and clinically advanced epigenetic-targeted therapies include azacitidine and decitabine, which inhibit DNA methylation through competitive inhibition of the enzymatic activity of the DNA methyltransferase family enzymes. Small molecules that disrupt oncogenic fusion protein activity and their associated chromatin complexes have demonstrated remarkable promise, and this approach has become the standard treatment for a subset of leukemias driven by the PML-RARA oncogenic fusion protein. A deeper understanding of the mechanisms that drive epigenetic dysregulation in pediatric cancer may hold the key to future success in this field, as the landscape of druggable epigenetic targets is also expanding.

P1/2, N=218, Active, not recruiting, AbbVie | Trial completion date: Dec 2024 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2026

P2, N=164, Active, not recruiting, Takeda | Trial completion date: Dec 2024 --> Mar 2025

P1, N=30, Recruiting, The First Affiliated Hospital of Xiamen University

We also conducted a conjoint analysis of the transcriptome and the m5C methylome of the full-length transcripts, uncovering several dysregulated mRNA isoforms. Collectively, our findings indicate that mRNA m5C methylation is implicated during AML progression, and AZA exhibits an overall suppressive effect on this process.

This study investigates the potential of Bentonite (BNT)-based nanoparticles (NPs) as drug carriers for azacitidine (AZA) in treating THP-1 and K562 myeloid leukemia (AML) cell lines, aiming to improve drug stability, bioavailability, and therapeutic efficacy while ensuring controlled release...BNT nanoparticles are promising carriers for AZA, enhancing targeted delivery, reducing side effects, and potentially lowering the required dose for leukemia treatment. These findings support further investigation into the clinical application of BNT-AZA in hematologic cancers.

The patient underwent four cycles of azacitidine (AZA) therapy, followed by successful bone marrow transplantation (BMT)...The patient was discharged 47 days postoperatively. This case demonstrated the rapid progression of infective endocarditis following BMT, highlighting the need for prompt recognition and management.

These results indicated that shRNA-mediated MBD2 knockdown suppresses HNSCC cell growth by upregulating p21 expression. In addition to its role as an oncogene, MBD2 may serve as a prognostic biomarker and therapeutic target for HNSCC patients.

Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.

He was initially diagnosed as donor-derived myelodysplastic syndrome (MDS) and treated with azacitidine, followed by secondary transplantation using unrelated BM, providing durable complete remission...DC-TAM is a rare UCBT-related complication which resembles MDS, but the identification of GATA1 mutation may be useful for its diagnosis. Our genetic analyses revealed that a pre-existing clone in UCB may contribute to the development of donor cell-derived hematologic neoplasms, highlighting the potential relevance of genetic screening of donor UCB.

Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine...Cells selected for stable acquired resistance to TUS exhibited increased BAX and hypersensitivity to venetoclax (1900-fold), navitoclax and MCL1 inhibitors. MV-4-11 FLT3-ITD clones expressing NRASG12D revealed that high-level expression of NRASG12D generated modest resistance to TUS and greater resistance to venetoclax (VEN), yet the TUS/VEN combination exhibited synergy in NRASG12D AML model. Favorable preclinical safety and pharmacology properties, the efficacy of the TUS/VEN combination in a murine model, and the synthetic lethal vulnerability to VEN that accompanies TUS resistance provide the basis for exploration of the TUS/VEN combination in patients with relapsed or refractory AML.

P1/2, N=6, Active, not recruiting, Thomas Jefferson University | Recruiting --> Active, not recruiting | N=37 --> 6

P3, N=48, Recruiting, Institut de Recherches Internationales Servier | Not yet recruiting --> Recruiting

To target this pathway, we investigated the activity of the potent chloroquine-derived autophagy inhibitor, Lys05, on human AML cells, patient samples, and patient derived xenograft models...Moreover, Lys05 overcame hypoxia-induced chemoresistance and improved the efficacy of cytarabine, venetoclax, and azacytidine in vitro and in vivo in AML models. Our results demonstrate the importance of autophagy, specifically mitophagy, as a critical survival and chemoresistance mechanism of AML cells under hypoxic marrow conditions. Therapeutic targeting of this pathway in future clinical studies for AML is warranted.

P2, N=45, Recruiting, University of Leipzig | Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Apr 2025

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups...Additional studies defining the prognostic role of measurable residual disease following VEN-based treatment have further advanced prognostication capabilities and increased the ability for close disease monitoring and early targeted intervention prior to morphologic relapse. This review summarizes these recent developments and their impact on the treatment and survival of transplant-ineligible patients living with AML.

These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

Three are still alive and are undergoing azacitidine treatment at 6.5, 8.5, and 21 months after their diagnosis.Identification of splicing factor gene mutations is an important diagnostic tool for the stratification of MDS patients...Other biological factors such as the mutation variant, association with complex karyotypes, and mutations in other genes, may also affect the prognosis of patients with mutated SF3B1. Therefore, a comprehensive view that includes all cytogenomic, molecular, and clinical data is important for accurate diagnosis and personalized treatment of MDS patients.Supported by MH CZ-DRO 0064165

Gilteritinib exhibited promising outcomes by targeting FLT3 receptors, offering a new treatment approach, and revealing improved overall survival compared to salvage chemotherapy in the difficult-to-treat patient population.

P4, N=44, Active, not recruiting, AbbVie | Trial completion date: Jul 2024 --> Apr 2025 | Trial primary completion date: Jul 2024 --> Apr 2025

Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

P1, N=20, Not yet recruiting, Baylor College of Medicine | Trial completion date: Oct 2028 --> Feb 2029 | Initiation date: Oct 2024 --> Feb 2025 | Trial primary completion date: Nov 2027 --> Mar 2028

P3, N=339, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

P2/3, N=76, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=146, Recruiting, Technische Universität Dresden | Not yet recruiting --> Recruiting

P1/2, N=18, Recruiting, Sanofi | Trial completion date: Feb 2029 --> Aug 2029

P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Jun 2024 --> Nov 2024

In particular, AKT1 phosphorylation behaved as a hallmark of the progression. Overall, we provided new insights on the characterization of 1qJT in SRSF2-mutated myeloid neoplasms and first showed that epigenetics is a powerful tool to investigate the molecular landscape of repetitive DNA rearrangements.

P1, N=14, Terminated, ALX Oncology Inc. | Phase classification: P1/2 --> P1 | N=97 --> 14 | Active, not recruiting --> Terminated; While intended to be a Phase 1/2 clinical study, the study never moved forward to Phase 2.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Trial completion date: Jun 2026 --> Jun 2027

P2, N=40, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting

The combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.

P2, N=60, Not yet recruiting, Technische Universität Dresden

P=N/A, N=20, Active, not recruiting, Centre Hospitalier Universitaire de Nice | Recruiting --> Active, not recruiting

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

P1/2, N=34, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=58 --> 34