decitabine

P1, N=30, Not yet recruiting, M.D. Anderson Cancer Center

Because the methods of determining maximum tolerated dose are not well suited to this paradigm, and because the mechanism of action, which is depletion of DNA methylase 1 (DNMT1), is complex and dependent on passing through a cell cycle, a pharmacodynamic assay that measures DNMT1 can inform clinical trials aimed at establishing and improving therapy. Herein, we provide an assay that measures DNMT1 relative levels in circulating T cells of peripheral blood.

P2, N=70, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2028 --> Feb 2028

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University

P2, N=60, Not yet recruiting, Chinese PLA General Hospital

The objective of this study is to assess the anti-cancer efficacy of trichostatin C (TSC), an analogue of trichostatin A sourced from the fermentation of Streptomyces sp...When combined with the DNMT inhibitor decitabine, TSC exhibits a synergistic anti-cancer effect...In conclusion, our findings suggest TSC as a promising anti-cancer agent with HDAC inhibitory activity. Furthermore, our results highlight the potential utility of TSC in combination with DNMT inhibitors for cancer treatment.

P1/2, N=54, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=90, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2025 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Sep 2023

P2, N=77, Recruiting, The First Affiliated Hospital of Soochow University

P1, N=2, Terminated, Joseph Jurcic | N=13 --> 2 | Trial completion date: Dec 2025 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Apr 2024; Closed by Sponsor

Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells...The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.

We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

P1/2, N=40, Suspended, Sclnow Biotechnology Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1/2, N=218, Active, not recruiting, ImmunoGen, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM)...Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.

In particular, mice bearing syngeneic 4T1 cancer showed higher tumor growth control when receiving the combinatorial treatment compared to single controls in association with a higher expression of MHC class I on cancer cells and reduction in Tregs within the tumor microenvironment. Furthermore, remodeling of the CD8+ T cell infiltration and cytotoxic activity toward cancer cells confirmed the effect of decitabine in enhancing anticancer vaccines in immunotherapy regimens.

P1, N=61, Active, not recruiting, Nkarta Inc. | Recruiting --> Active, not recruiting | N=90 --> 61

NCOR1::GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

P2, N=80, Recruiting, Mayo Clinic | N=55 --> 80

Our findings reveal that heightened Dnmt3a expression induces hypermethylation of the CGI at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine (DAC) and trichostatin A (TSA) emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.

P1, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jul 2024

Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL.

The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.

P2, N=132, Terminated, Technische Universität Dresden | N=238 --> 132

P2, N=23, Not yet recruiting, Northside Hospital, Inc.

P2, N=33, Active, not recruiting, Johns Hopkins University | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Sep 2024

P3, N=126, Active, not recruiting, Sellas Life Sciences Group | Recruiting --> Active, not recruiting

P1/2, N=70, Terminated, Kartos Therapeutics, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jul 2024 --> Sep 2023 | Active, not recruiting --> Terminated; In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.

CAP combined with decitabine induced Caspase-3 activation, which cleaved decitabine-upregulated GSDME and ediated pyroptosis.

P2, N=25, Recruiting, University of Washington | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2026

P2, N=50, Recruiting, Children's Hospital of Soochow University

P2, N=21, Active, not recruiting, National Cancer Institute (NCI)

This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.

P1, N=15, Active, not recruiting, National Cancer Institute (NCI)

P1, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=37, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2024

Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%). These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.

Our work provides clear a understanding of immunogenic cell death triggered by mitochondria-targeted PDT, offering a new approach for enhancing the efficacy of PD-1 blockade in CRC.

P1, N=13, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=120, Recruiting, First Affiliated Hospital of Zhejiang University | Not yet recruiting --> Recruiting