decitabine

P2, N=30, Recruiting, The First Affiliated Hospital of Soochow University | Not yet recruiting --> Recruiting

Finally, we highlight some of the ongoing studies that test quizartinib in patients with FLT3-ITD-positive AML, patients with FLT3-ITD-negative AML, in both the first-line and R/R settings, in patients fit or unfit for intensive chemotherapy, including studies for quizartinib-based combination with other compounds such as decitabine and venetoclax. Future research should aim to further optimize the clinical value of quizartinib and explore its use in additional clinical settings, which could be achieved by testing quizartinib with other drugs, better characterization of the mechanisms of resistance, identification of the role of quizartinib as a maintenance therapy after allo-HCT, and investigating quizartinib in patients with FLT3-ITD-negative AML.

P1/2, N=20, Not yet recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=75, Completed, University of Nebraska | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> Mar 2024

P2, N=59, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

P=N/A, N=76, Recruiting, Ningbo First Hospital; Ningbo First Hospital

P2, N=101, Active, not recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting --> Active, not recruiting | Trial completion date: May 2024 --> Apr 2026 | Trial primary completion date: May 2024 --> Oct 2024

P1, N=20, Recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

Herein, an injectable hydrogel-encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical-grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti-tumor immune response...The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis-based and injectable hydrogel-aided strategies for preventing the postoperative recurrence of TNBC.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=18, Recruiting, The First Affiliated Hospital of Xiamen University

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Furthermore, DAC + DOX@FPSD NP treatment could promote pyroptosis-associated antitumor immunity, as evidenced by the increased presence of CD3+, CD4+, and CD8+ T cells, heightened secretion of tumor necrosis factor-α and interferon-γ, elevated high-mobility group box-1 levels, and enhanced calreticulin exposure. The FPSD nanocarrier developed in this study had favorable stability, active targeting ability, biocompatibility, and controlled release properties, and the DAC + DOX@FPSD NPs represented an approach to antitumor therapy by inducing pyroptosis, which offers a promising avenue for breast cancer treatment.

Our findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.

P2, N=39, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Future research should incorporate larger sample sizes and advanced genomic techniques like RNA sequencing to better understand oncogenic mechanisms. The study emphasizes the need for further in situ analyses of decitabine's efficacy, setting the foundation for future neuro-oncological treatments.

A metronomic, low-dose schedule of decitabine and Venetoclax was safe and effective in myeloid malignancies with few dose reductions or interruptions in an older diverse population. Median OS for AML and TP53 mutated patients was 16.1 and 11.3 months respectively.

The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted.

No abstract available

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

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

P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=270, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=106, Not yet recruiting, Jiangsu Province Hospital; Jiangsu Province Hospital

P1/2, N=54, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

P2, N=45, Not yet recruiting, M.D. Anderson Cancer Center

The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.

We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.

An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment.Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672.

Given the lack of effective therapies in myelofibrosis with severe cytopenias, this study supports further investigation into the use of hypomethylating agents as single agents or in combination therapies. NCT00095784.

Hypomethylating agents like azacitidine and decitabine have shown promise in improving relapse-free and overall survival, particularly in older patients with AML ineligible for transplantation. Combination regimens involving azacitidine and venetoclax have demonstrated encouraging outcomes post-hematopoietic stem cell transplantation. Targeted therapies, particularly FLT3 inhibitors like midostaurin and quizartinib, have shown significant benefits in improving survival outcomes, especially in FLT3-mutated AML cases. Gilteritinib and sorafenib also exhibit the potential to reduce relapse rates post-transplant. Isocitrate dehydrogenase inhibitors, including ivosidenib and enasidenib, present novel options for postchemotherapy and posttransplantation maintenance...The approval of oral azacitidine represents a significant advancement, emphasizing the need for further investigation into personalized maintenance approaches. In conclusion, the evolving landscape of maintenance therapy and integrating targeted therapies in AML offers promising avenues for improving patient outcomes.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=58, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P1/2, N=78, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Aug 2024

Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.

P1, N=241, Completed, Novartis Pharmaceuticals | Phase classification: P1b --> P1

The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and β2-MG, and detection of serum CysC and β2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.

P2, N=70, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2027 --> Feb 2028