This phase I trial tests the safety, side effects, and best dose of lintuzumab-Ac225 in combination with venetoclax and ASTX-727, and how well they work in treating patients with newly diagnosed acute myeloid leukemia (AML). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called actinium Ac 225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers actinium Ac 225 to kill them. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. ASTX-727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving lintuzumab-Ac225 in combination with venetoclax and ASTX-727 may be safe and tolerable in treating patients with newly diagnosed AML and may improve the chance of going into remission and staying in remission for a longer period of time.

开始日期2026-04-21

申办/合作机构

National Cancer Institute

NCT07153497

/ Not yet recruiting临床2期IIT

A Randomized Phase 2 Trial of Olutasidenib-Based Therapies in Patients With Newly Diagnosed IDH1-Mutant Myeloid Malignancies: A MyeloMATCH Substudy

This phase II MyeloMATCH treatment substudy tests the addition of olutasidenib to usual treatment in patients with higher-risk myelodysplastic syndrome (MDS) or patients with acute myeloid leukemia (AML) with a mutation in the IDH1 gene. Olutasidenib blocks the protein made by the mutated IDH1 gene. Blocking this protein may help keep cancer cells from growing. For patients with MDS, olutasidenib will be added to decitabine-cedazuridine (also called ASTX727). Decitabine is in a class of medications called hypomethylating agents and is the standard treatment for MDS. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The cedazuridine makes it possible to take the decitabine by mouth. Adding olutasidenib to the usual treatment for MDS (ASTX727) may increase the likelihood of going into remission. For patients with AML, olutasidenib and ASTX727 will be combined with venetoclax, a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Adding olutasidenib to the usual treatment for AML (ASTX727 and venetoclax) may increase the likelihood of going into remission. For low risk MDS, the substudy tests whether giving olutasidenib alone helps improve blood counts.

开始日期2026-02-26

申办/合作机构

National Cancer Institute

NCT06661915

/ Recruiting临床2期IIT

A Randomized Phase 2 Trial of ASTX727 +/- Iadademstat in Accelerated/Blast-Phase Philadelphia Chromosome-Negative Myeloproliferative Neoplasms (MPNs)

This phase II trial compares the effect of ASTX727 in combination with iadademstat to ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). ASTX727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with iadademstat may be more effective than ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative MPNs.

开始日期2026-02-03

申办/合作机构

National Cancer Institute

100 项与地西他滨/西达尿苷相关的临床结果

登录后查看更多信息

100 项与地西他滨/西达尿苷相关的转化医学

登录后查看更多信息

100 项与地西他滨/西达尿苷相关的专利（医药）

登录后查看更多信息

项与地西他滨/西达尿苷相关的文献（医药）

2025-08-01·Lancet Haematology

Oral decitabine and cedazuridine maintenance after haematopoietic stem-cell transplantation in very high-risk acute myeloid leukaemia or myelodysplastic syndrome (GFM-DACORAL-DLI): a multicentre, single-arm, phase 2 trial

Article

作者: de Latour, Régis Peffault ; Chevret, Sylvie ; Charbonnier, Amandine ; Chermat, Fatiha ; D'Aveni, Maud ; Carre, Martin ; Thépot, Sylvain ; Labussière, Hélène ; Stamatoullas, Aspasia ; Mokeddem, Chama ; Petit, Raphael ; Ravinet, Aurélie ; Rubio, Marie-Thérèse ; Paul, Franciane ; Adès, Lionel ; Alani, Mustafa ; Huynh, Anne ; Raffoux, Emmanuel ; Chevallier, Patrice ; Sébert, Marie ; Desseaux, Kristell ; Robin, Marie ; Garnier, Alice ; Mediavilla, Clémence ; Himberlin, Chantal ; Fenaux, Pierre

BACKGROUND:

The combination of a hypomethylating agent with donor lymphocyte infusion as maintenance therapy after haematopoietic stem-cell transplantation (HSCT) in acute myeloid leukaemia and myelodysplastic syndrome might reduce the risk of relapse. We aimed to evaluate the activity and safety of oral decitabine and cedazuridine (ASTX727) as maintenance after allogeneic HSCT in patients with acute myeloid leukaemia or myelodysplastic syndrome at very high risk of relapse post-transplantation.

METHODS:

We conducted a multicentre, single-arm, phase 2 study (GFM-DACORAL-DLI) at 12 centres in France. We enrolled patients aged 18-70 years with an Eastern Cooperative Oncology Group performance status of 0-2, without contraindication for HSCT, and with very high-risk disease (poor or very poor prognosis according to the revised International Prognostic Scoring System for myelodysplastic syndrome, adverse risk according to the 2017 European LeukemiaNet classification for acute myeloid leukaemia; unfavourable genetics; and acute myeloid leukaemia post-myelodysplastic syndrome or post-myeloproliferative neoplasm, or relapsing less than 2 years after complete response). Patients were included 5-45 days before transplantation. ASTX727 was orally administered at escalating doses (100 mg cedazuridine plus 35 mg decitabine starting at 1 day per cycle and increasing to 3 days) from day 40 post-HSCT, up to ten cycles. Donor lymphocyte infusion was recommended when patients had no contraindication after cycle 4. The primary endpoint was disease-free survival at 1 year after HSCT, assessed in the first 28 enrolled patients treated with ASTX7277. Safety was assessed in all participants who received at least one course of ASTX727. This study was registered with ClinicalTrials.gov (NCT04857645); enrolment is complete but follow-up is ongoing.

FINDINGS:

Between Sept 28, 2021, and March 1, 2023, 59 patients were screened and 51 patients underwent allogeneic HSCT (median age 62·0 years [IQR 56·5-65·0]; 22 [43%] female, 29 [57%] male). 34 patients received maintenance treatment with ASTX727; seven of them received at least one donor lymphocyte infusion. 14 (41%) patients completed the ten cycles. Median follow-up was 12·6 months (IQR 10·3-14·3). Among the first 28 enrolled patients treated with ASTX727, disease-free survival at 1 year after HSCT was 70·4% (95% CI 55·1-89·9). The most frequent grade 3 or worse adverse events were haematological, occurring in 25 (74%) of 34 patients (21 [62%] neutropenia, eight [24%] thrombocytopenia, four [12%] anaemia). Serious adverse events occurred in 14 (41%) of 34 patients, and were haematological in eight patients and gastrointestinal in three patients. One treatment-related death, due to thrombocytopenia, occurred.

INTERPRETATION:

ASTX727 could be a potential treatment option after HSCT in patients with acute myeloid leukaemia or myelodysplastic syndrome at very high risk of relapse. Further investigation is warranted to establish the efficacy and safety of this therapeutic approach.

FUNDING:

Taiho Oncology and Astex Pharmaceuticals.

2025-07-01·CURRENT OPINION IN ONCOLOGY

Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms?

Review

作者: Hendlisz, Alain ; Meyers, Michel ; Karfis, Ioannis

Purpose of review:

The purpose of this review is to evaluate the role of epigenetic-targeting approaches in the management of neuroendocrine neoplasms (NENs), particularly as a priming strategy for subsequent therapies. We explore the molecular basis of epigenetic modifications in NENs, and we review preclinical and clinical studies on DNA methyltransferase and histone deacetylase (HDAC) inhibitors.

Recent findings:

DNA methyltransferase and HDAC inhibitors can upregulate SSTR2 expression, thereby improving radioligand uptake and treatment response in NENs. The LANTana study investigates ASTX727 as a strategy to restore SSTR2 expression in metastatic NENs, allowing previously ineligible patients to receive PRRT. Preclinical studies demonstrate that combining epigenetic agents with radiotherapy, chemotherapy, or targeted inhibitors can enhance tumour sensitivity and overcome resistance.

Summary:

Epigenetic modifications play a crucial role in NENs, influencing tumour progression, therapy resistance, and SSTR2 expression. Epigenetic priming with DNA methyltransferase and HDAC inhibitors can enhance SSTR2 expression, improving the efficacy of PRRT in NENs. The LANTana study and other trials are investigating whether epigenetic-targeting approaches can be integrated into NEN treatment to optimize PRRT and overcome therapeutic limitations.

2024-11-01·BRITISH JOURNAL OF HAEMATOLOGY

Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study

Article

作者: Novák, Jan ; Sano, Yuri ; Illes, Arpad ; Santini, Valeria ; Fracchiolla, Nicola Stefano ; Keating, Mary‐Margaret ; Metzelder, Stephan K. ; Lübbert, Michael ; Lunghi, Monia ; Rodríguez‐Macías, Gabriela ; Platzbecker, Uwe ; Oganesian, Aram ; Arnan, Montserrat ; Mayer, Jiří ; del Castillo, Teresa Bernal ; Krauter, Jürgen ; Koristek, Zdenek ; Geissler, Klaus ; Keer, Harold

Summary:

This study compared decitabine exposure when administered IV (DEC‐IV) at a dose of 20 mg/m2 for 5‐days with orally administered decitabine with cedazuridine (DEC‐C), as well as the clinical efficacy and safety of DEC‐C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC‐IV or oral DEC‐C (days 1–5 in a 28‐day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC‐C for subsequent treatment cycles until treatment discontinuation. Equivalent systemic decitabine exposures were demonstrated (5‐day area under the curve ratio between the two decitabine formulations of 99.64 [90% confidence interval 91.23%, 108.80%]). Demethylation rates also were similar (≤1.1% difference). Median overall survival (OS), clinical response and safety profile with oral DEC‐C were consistent with those previously observed with DEC‐IV. Next‐generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC‐C in patients with AML.

项与地西他滨/西达尿苷相关的新闻（医药）

2025-09-11

·GlobeNewswire-Health Care

Biosplice Therapeutics Announces First Patient Dosed in NCI-Sponsored Clinical Trial of Cirtuvivint in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Sept. 09, 2025 -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering advancements in small molecule inhibition of CDC-like kinases (CLK) and Dual-specificity tyrosine phosphorylation-regulated (DYRK) kinases, today announced that the first patient has been dosed in a Phase 1 clinical trial of cirtuvivint in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and conducted by the NCI funded Experimental Therapeutics Clinical Trials Network, under a Cooperative Research and Development Agreement (CRADA) with Biosplice. This milestone highlights the ongoing collaboration between Biosplice and the NCI’s Cancer Therapy Evaluation Program (CTEP). The trial (NCT06484062) is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cirtuvivint, both as a monotherapy and in combination with ASTX727 (INQOVI, oral decitabine/cedazuridine), a hypomethylating agent developed by Taiho Oncology, Inc. and FDA-approved for MDS. The study is enrolling patients with relapsed or refractory AML or MDS, and is led by Principal Investigator Dr. Evan Chen at Dana-Farber Cancer Institute. “We are pleased to see continued momentum in cirtuvivint’s development with this important milestone in our collaboration with the NCI,” said Yusuf Yazici, M.D., Chief Medical Officer at Biosplice. “AML and MDS remain areas of significant unmet need, and we are hopeful that cirtuvivint’s unique mechanism, modulating RNA splicing to disrupt oncogenic signaling, will demonstrate benefit for patients with these challenging malignancies. The combination with a well-established agent such as ASTX727 offers a compelling approach to enhancing therapeutic response.” Cirtuvivint is a selective pan-CLK, pan-DYRK inhibitor that modulates alternative RNA splicing, including transcripts involved in oncogenic pathways. Preclinical studies have shown that CLK/DYRK inhibition alters splice patterns in malignant cells, suppresses oncogenic variants, and enhances apoptosis. The combination with ASTX727 aims to leverage two complementary mechanisms, hypomethylation (ASTX727) and splicing modulation (cirtuvivint), to target leukemic cells more effectively.、 In addition to the NCI-sponsored AML/MDS trial, cirtuvivint is being evaluated in several other clinical programs: An ongoing Phase 2 trial in advanced soft tissue sarcomas (NCT05633307) An upcoming combination trial with olaparib in BRCA-mutated or homologous recombination-deficient platinum-resistant ovarian cancer (NCT06856499) An upcoming combination trial with irinotecan in relapsed small-cell lung cancer (NCT07155200) Cirtuvivint is a small molecule inhibitor of CLK and DYRK kinases, which are increasingly recognized as key drivers of various cancers. By targeting these kinases, cirtuvivint modulates alternative pre-mRNA splicing, which reduces the expression of genes vital for tumor growth, survival, and drug resistance. The compound has shown broad anti-tumor activity across a range of solid and liquid tumors in extensive preclinical studies. Cirtuvivint has also been investigated for the treatment of advanced solid tumors in two clinical trials. The first, SM08502-ONC-01 (NCT03355066), was a first-in-human dose escalation study designed to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors. The second, SM08502-ONC-03 (NCT05084859), was a Phase 1b trial assessing the efficacy of cirtuvivint in combination with standard treatments for patients with advanced castration-resistant prostate cancer, advanced non-small cell lung cancer, and advanced colorectal cancer. Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for knee osteoarthritis (completed Phase 3) and cirtuvivint for numerous cancers, with a broad preclinical pipeline that encompasses Alzheimer’s disease, diabetes, and other degenerative conditions. The content above comes from the network. if any infringement, please contact us to modify.

临床研究

2025-07-12

·ioncology

2025 BOC/BOA丨姜尔烈教授解析AML治疗最新突破：全口服方案与Menin抑制剂的研究进展

点击蓝字关注我们编者按：2025年中国临床肿瘤学会年度进展研讨会（BOC）暨Best of ASCO 2025 China（BOC/BOA）于7月4日至5日在南京盛大召开。此次会议汇聚了国内外肿瘤学领域的顶尖专家，共同回顾并探讨过去一年中国临床肿瘤学的重大进展，并分享刚刚落幕的美国临床肿瘤学会（ASCO）年会的前沿成果。在本次会议中，CSCO白血病专委会主任委员、中国医学科学院血液病医院（中国医学科学院血液学研究所）姜尔烈教授分享了两项急性髓系白血病（AML）领域的突破性研究，并在接受采访时进一步解读了这两项研究的重要意义与临床价值。重磅研究一地西他滨-西达尿苷（DEC-C）联合维奈克拉（VEN）全口服方案用于不适合强化诱导化疗的新诊断急性髓系白血病（AML）患者：来自101例患者的Ⅱ期队列研究结果（摘要号：6504)背景：对于年龄≥75岁且不适合接受诱导化疗的AML患者，BCL-2抑制剂维奈克拉（VEN）联合阿扎胞苷（AZA）已获批准，该批准基于III期VIALE-A临床试验（完全缓解率[CR]为36.7%；中位CR持续时间为17.5个月；中位总生存期[OS]为14.7个月）。然而，患者需每月接受为期7天的阿扎胞苷静脉注射直到疾病进展，这给患者带来了较大负担。此外，多项校正后比较研究显示，阿扎胞苷与地西他滨的临床疗效相似。口服DEC-C（地西他滨35 mg，塞西达尿苷100 mg）的药代动力学（PK）曲线下面积与静脉注射地西他滨相当。本项Ⅰ/Ⅱ期临床试验旨在评估口服DEC-C联合维奈克拉治疗年龄≥75岁或因合并症无法接受一线强化诱导化疗的AML患者（NCT04657081）。本文报告了该试验Ⅱ期部分的结果。方法：符合条件的患者在28天周期内接受口服DEC-C（1-5天）和维奈克拉400 mg/d治疗，第一周期维奈克拉剂量逐步增加（第1天100 mg，第2天200 g，第3天及之后400 g）。第一周期骨髓检查为可选，依据疗效和血细胞恢复情况调整维奈克拉和/或DEC-C的剂量。主要终点为完全缓解（CR）率，基于欧洲白血病网（ELN）2017年的疗效标准。结果：截至2024年9月30日，共有101名患者入组并完成了中位4个周期（范围：1-15周期）治疗。患者中位年龄为78岁。根据ELN 2017年分类，预后良好、中等和不良的患者分别占31.7%、33.7%和29.7%。中位随访时间为11.2个月。CR率和CR/CR伴不完全血液学恢复率分别为46.5%（95%CI：36.5%–56.7%）和63.4%（95%CI：53.2%–72.7%）。中位CR达成时间为2.4个月。中位CR持续时间未达到；在达到CR的患者中，80.0%在6个月时保持CR，75.3%在12个月时保持CR。中位总生存期为15.5个月（95% CI：7.6–无法估算）。98.0%的患者报告了≥3级的治疗相关不良事件，最常见的是发热性中性粒细胞减少症（49.5%）、贫血（38.6%）和中性粒细胞减少症（35.6%）。30天和60天死亡率分别为3.0%和9.9%。药代动力学数据显示口服DEC-C与维奈克拉之间不存在药物相互作用。结论：对于不适合接受强化诱导化疗的初诊AML患者，DEC-C联合VEN的全口服方案与静脉注射阿扎胞苷联合维奈克拉方案的安全性、缓解率和生存率相当。这些数据支持DEC-C联合维奈克拉可作为该类患者的治疗选择。专家解读姜尔烈教授：该方案是目前首个用于急性髓系白血病（AML）患者，特别是老年AML患者的全口服治疗方案。根据目前Ⅱ期研究结果，该方案的血液学缓解率接近50%，而整体缓解率则更高，接近70%。研究中入组的患者均为老年人，且中位年龄超过70岁。疗效方面，研究显示该方案能够实现显著的缓解，并且在生存期方面也表现出显著的临床获益，患者的中位总生存期达到15个月以上。在安全性方面，患者的主要不良反应为血液学毒性，三级及以上的血小板减少和中性粒细胞减少的发生率约为20%，这一数据表明，从安全性角度来看，该治疗方案具有较好的耐受性。重磅研究二Ziftomenib治疗复发/难治性（R/R）NPM1突变急性髓系白血病（AML）：来自关键性KOMET-001研究的Ⅰb/Ⅱ期临床活性与安全性结果（摘要号：6506）背景：NPM1突变（NPM1-m）约占急性髓系白血病（AML）患者的30%。尽管目前已有风险分层方法，但近一半的患者会在一年内发展为复发/难治性（R/R）疾病，且此时化疗后的完全缓解（CR）率不足10%。Ziftomenib是一种强效、高选择性、口服、在研的Menin抑制剂，在单药治疗和联合治疗中对成人R/R NPM1突变和KMT2A重排AML患者表现出临床活性，600 mg/d作为NPM1突变单药治疗的Ⅱ期推荐剂量。本文展示了在关键性KOMET-001研究中，接受Ziftomenib单药治疗的NPM1突变患者的初步分析结果。方法：KOMET-001（NCT04067336）是一项多中心、开放标签的Ⅰ期/Ⅱ期研究，评估Ziftomenib在成人R/R AML患者中的疗效。在Ⅱ期中，NPM1突变的R/R AML患者接受Ziftomenib 600 mg 每日一次治疗。Ⅱ期的主要终点为完全缓解伴完全/部分血液学恢复（CR/CRh）；关键次要终点为复合完全缓解（CRc）、CR/CRh和CRc的持续时间以及安全性。以下分析包括来自Ⅰb/Ⅱ期的NPM1突变患者数据。结果：Ⅱ期的主要终点已达成（P=0.0058）。截至2024年12月20日，Ⅰb/Ⅱ期研究共入组112名患者（51%来自美国/加拿大，49%来自欧洲/英国），并接受Ziftomenib 600 mg每日一次治疗，中位随访时间为4.2个月。患者中位年龄为69岁（范围：22–86岁），56%为女性，83%为ECOG表现状态评分0–1，既往治疗中位数为2次（范围：1–7），其中60%的患者既往接受过维奈克拉（VEN）治疗，23%的患者既往接受过移植治疗。在所有Ⅰb/Ⅱ期患者中，CR/CRh率为25%（28/112；95% CI：17-34），总缓解率为35%（39/112；95%CI：26-44）。在Ⅱ期研究中，23%（21/92；95% CI：15-33）患者达到了CR/CRh。在接受检测的CR/CRh应答患者中，67% (10/15) 的微小残留病 (MRD) 阴性。无论是否接受过VEN治疗，CR/CRh率均较为相似（VEN初治组21% vs. VEN暴露组24%）。Ziftomenib耐受性良好，3%（3/112）患者因治疗相关不良事件（TRAEs）中断治疗。40%（45/112）患者出现≥3级TRAEs，常见的不良事件包括13%的分化综合征（均为3级），贫血、发热性中性粒细胞减少症和血小板减少症各≤5%，以及2%的QTc延长（3级）。将呈现更新的临床活性和安全性数据。结论：在关键性KOMET-001研究中，Ⅱ期的主要终点已达成：Ziftomenib在R/R NPM1突变AML患者中取得了深度且持久的疗效，无论是否曾接受过VEN治疗。Ziftomenib耐受性良好，造血抑制有限，且仅有3%的患者因Ziftomenib相关不良事件中断治疗。综合这些数据，支持Ziftomenib单药治疗作为R/R NPM1突变AML患者的新治疗选择的潜力。专家解读姜尔烈教授：该研究讨论了Menin抑制剂的单药治疗，其CR率也表现出较好的效果，超过了20%，接近30%。目前，该药物正计划开展Ⅲ期临床研究，探索其与维奈克拉、阿扎胞苷的联合应用，或与经典的3+7方案联合使用。这项Ⅲ研究尤其是Menin抑制剂与维奈克拉或阿扎胞苷的联合应用有很大潜力。通过三药联合，预计可以进一步提高缓解率。今天的讨论主要集中在难治复发患者的治疗，但后续临床研究主要针对初治患者。预计在这一群体中，Menin抑制剂联合其他药物的治疗方案将取得更高的缓解率。目前其他分子靶向药物，如FLT3 抑制剂、IDH抑制剂、RAS抑制剂和Menin抑制剂等，联合低强度化疗在未来可能成为一种替代传统化疗的策略。这些药物的联合使用不仅可能提高一线治疗的缓解率，还能降低诱导治疗相关的死亡率，改善患者的安全性。因此，小分子靶向药物与非细胞毒药物的联合应用，已然成为当前研究的热点领域。未来，这类联合方案有望发展为可替代传统细胞毒治疗的安全有效方案，为AML的治疗带来新的变革。专家简介姜尔烈教授中国医学科学院血液病医院（中国医学科学院血液学研究所）干细胞移植中心主任医学博士、主任医师、博士生（后）导师中国初级卫生保健基金会造血干细胞移植专委会主任委员CSCO白血病专委会主任委员中国血液病专科联盟白血病自体移植协作组组长中华医学会血液学分会造血干细胞应用学组副组长中国抗癌协会血液肿瘤专业委员会常务委员，造血干细胞移植与细胞治疗学组副组长CSCO自体造血干细胞移植工作组副组长天津市抗癌协会常务理事天津市血液与再生医学学会副理事长《中华血液学杂志》、《白血病·淋巴瘤》等杂志编委（来源：《肿瘤瞭望–血液时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议临床结果临床2期CSCO会议临床3期

2025-07-10

·PRNewswire

Can Early Intervention Prevent Leukemia? New Trial Gives Patients a Choice Beyond the Current 'Wait and See' Approach

Scientists are exploring if early intervention can prevent AML in high-risk patients, shifting the focus from monitoring to proactive prevention. CAMBRIDGE, Mass., July 10, 2025 /PRNewswire/ -- Break Through Cancer, a Boston-based cancer research foundation, has launched a clinical trial to evaluate the feasibility of early intervention for Clonal Hematopoiesis (CH), a precursor to acute myeloid leukemia (AML). This multi-institutional study focuses on high-risk patients, exploring a new approach to managing this pre-malignant condition and advancing the groundwork for preventing this aggressive blood cancer. Understanding CH and AML Risk Continue Reading Break Through Cancer launches study to test early action against AML Post this AML is a malignant blood disorder characterized by the rapid production of abnormal myeloid cells in the bone marrow and bloodstream. This aggressive cancer disrupts normal blood cell production and is associated with severe clinical outcomes, including a five-year survival rate of approximately 30%. CH can occur naturally with aging or as a consequence of chemotherapy or radiation treatment. Before receiving an AML diagnosis, many patients already have CH with AML-associated mutations, making it a pre-malignant condition. While often symptomless, some individuals with CH may have low blood counts—a condition known as Clonal Cytopenia of Uncertain Significance (CCUS). Those with high-risk CCUS have a greater than 50% chance of progressing to AML within five years. "A lot of patients have already survived one cancer, and it's devastating when they receive a diagnosis of a therapy-related AML. The ability to potentially target the disease before it progresses to that point is what really excites me," said Dr. Kelly S. Chien, Assistant Professor at The University of Texas MD Anderson Cancer Center and a clinician on the study. A New Approach: Early Intervention As part of the new interventional trial, patients diagnosed with high-risk CCUS have the opportunity to choose proactive treatment for their precursor condition. The trial (NCT06802146) will evaluate Inqovi (Astex Pharmaceuticals) in patients with high-risk CCUS, assessing the safety and feasibility of intervention at this precursor stage. Inqovi—an oral drug currently FDA-approved to treat a related blood cancer—works by altering the DNA of abnormal blood cells, thus slowing their growth and reducing the risk of progression to more advanced disease stages. The two-arm study will enroll patients with high-risk CCUS who opt for one year of treatment with Inqovi or observation only. "Many patients feel anxious when given a CCUS diagnosis and information about AML risk," says Dr. Lachelle Weeks, Assistant Professor, Dana-Farber Cancer Institute and a clinician on the study. "There are a number of patients who want to do something about it, and this trial could be the first step." All patients will be observed for three years to assess the effects of Inqovi on AML progression and other health outcomes. "Patients with high-risk CCUS already have low blood counts, which can significantly affect their quality of life," said Dr. Chien. "We're also looking at whether treatment improves quality of life, stabilizes blood counts, or reduces the burden of comorbidities, like heart disease, that are sometimes associated with certain mutations." The trial will also assess mutational burden—whether the percentage of cells with mutations increases, decreases, or stays the same with treatment. A comparison of treated and untreated patients will provide insights into potential benefits of early intervention in CCUS. This trial aims to pave the way for future larger studies testing the efficacy of intervention as part of developing comprehensive AML prevention strategies. "The ultimate goal is to prevent diagnoses like AML altogether," Dr. Weeks notes. "This trial represents a critical step in understanding CCUS progression and exploring how early intervention could redefine care standards. If successful, it could spare patients and their families the profound challenges of living with and treating AML." Prioritizing Diversity in Cancer Research In addition to its scientific goals, this trial centers inclusivity in cancer research. By leveraging Break Through Cancer's model of radical collaboration and tapping into the broad reach of four disparate communities, this trial seeks to recruit a diverse and representative patient population and proactively circumvent long-standing inequities in cancer prevention research. "By recruiting from community sites and reflecting the demographics of our catchment areas, we're ensuring our findings benefit all populations at risk," says Dr. Weeks. To achieve this, the trial partners with community-based nurse navigators linked to Break Through Cancer's four partner sites. Together, researchers at Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and MD Anderson are working to close gaps in care and improve outcomes for all patients. About the trial Title: Early Intervention in High Risk CCUS (NCT06802146) About Break Through Cancer Founded in 2021, Break Through Cancer empowers outstanding researchers and physicians to both intercept and find cures for several of the deadliest cancers by stimulating radical collaboration among outstanding cancer research institutions, including its founding partners: Dana-Farber Cancer Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Memorial Sloan Kettering Cancer Center, MIT's Koch Institute for Integrative Cancer Research, and The University of Texas MD Anderson Cancer Center. The Foundation is supported by a Board of Directors from the five partner institutions and a Scientific Advisory Board of U.S. cancer experts. The Foundation was launched with an extraordinary challenge pledge of $250 million from Mr. and Mrs. William H. Goodwin, Jr. and their family, and the estate of William Hunter Goodwin III. For further information, please visit the Foundation's website at . References Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). Weeks LD, Ebert BL. Causes and consequences of clonal hematopoiesis. Blood. 2023;142(26):2235-2245. Savona M, Bewersdorf JP, Allen SL, et al. FDA approval summary: decitabine and cedazuridine tablets for myelodysplastic syndromes. Clin Cancer Res. 2022;28(16):3411-3414. Media Contact: Soracha Ward [email protected] SOURCE Break Through Cancer WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床研究上市批准

100 项与地西他滨/西达尿苷相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	地西他滨/西达尿苷	L01XY	DB15694

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
急性髓性白血病	欧盟	Otsuka Pharmaceutical Netherlands B.V.	2023-09-15
急性髓性白血病	冰岛	Otsuka Pharmaceutical Netherlands B.V.	2023-09-15
急性髓性白血病	列支敦士登	Otsuka Pharmaceutical Netherlands B.V.	2023-09-15
急性髓性白血病	挪威	Otsuka Pharmaceutical Netherlands B.V.	2023-09-15
慢性粒单核细胞白血病	澳大利亚	Otsuka Australia Pharmaceutical Pty Ltd.	2020-10-29
骨髓增生异常综合征	美国	Taiho Oncology, Inc.	2020-07-07

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
难治性贫血	临床3期	美国	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	奥地利	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	加拿大	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	捷克	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	法国	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	德国	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	匈牙利	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	意大利	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	西班牙	Astex Pharmaceuticals, Inc.	2018-02-15
难治性贫血	临床3期	英国	Astex Pharmaceuticals, Inc.	2018-02-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04340843 (ETCTN/NCI 10330, CTgov)	临床2期	软骨肉瘤 \| 中枢神经系统肿瘤 \| 脑转移瘤	19	ASTX727+Belinostat (Treatment (Belinostat, ASTX727))	遞衊夢鑰範衊膚衊鏇壓 = 鑰餘簾夢獵製築獵艱夢鹽齋範鏇廠蓋膚蓋衊窪 (醖鑰醖餘壓網範製構淵, 製願鬱鏇鏇糧齋鑰糧膚 ~ 製獵鹹壓網膚艱鏇襯窪) 更多	-	2025-09-16
NCT04340843 (ETCTN/NCI 10330, CTgov)	临床2期	软骨肉瘤 \| 中枢神经系统肿瘤 \| 脑转移瘤	19	SGI-110+Belinostat (Treatment (Belinostat, SGI-110))	衊糧築壓範網襯製壓積 = 願鏇繭衊範觸網衊憲鹹遞衊願糧繭獵壓醖廠獵 (觸網壓製夢窪餘構醖積, 淵鹽糧膚淵觸簾鹽遞鏇 ~ 鏇遞艱獵製簾醖夢憲選) 更多	-	2025-09-16
NCT04657081 (ASCO2025) 人工标引	临床2期	急性髓性白血病一线	101	decitabine-cedazuridine (DEC-C)+venetoclax	醖鏇襯齋夢膚積鹹願憲(蓋鹹鹽鬱鹽顧壓齋夢憲) = 衊鹹齋網膚醖製願餘襯鏇蓋願襯餘築衊淵壓鹽 (膚遞糧構範廠鬱範窪範, 36.5 ~ 56.7) 更多	积极	2025-05-23
NCT04657081 (S135, EHA2025)	临床1/2期	急性髓性白血病	189	DECITABINE-CEDAZURIDINE (DEC-C) (DEC-C + VEN)	鹽獵艱築衊糧壓繭鑰醖(壓餘醖艱窪窪艱觸襯鑰) = 窪鏇糧繭鹽醖顧顧蓋積衊鹽範鹽選簾範鏇壓獵 (壓選獵餘艱壓衊鑰簾蓋, 36.5 ~ 56.7) 更多	积极	2025-05-14
NCT05010772 (4277, ASH2024)	临床1期	急性髓性白血病 complex cytogenetics \| antecedent MDS/MPN \| therapy-related AML ... 更多	31	ASTX727 alone	餘築鑰夢鬱衊蓋齋糧積(夢鏇鹹觸夢築遞願顧範) = 襯遞獵廠糧獵醖製遞鹽範鬱廠積餘簾夢製窪簾 (遞窪糧簾醖鹽膚網製積 ) 更多	积极	2024-12-09
NCT05010772 (4277, ASH2024)	临床1期		31	ASTX727 plus venetoclax	餘築鑰夢鬱衊蓋齋糧積(夢鏇鹹觸夢築遞願顧範) = 鹹鑰襯鑰鏇鹽憲網蓋網範鬱廠積餘簾夢製窪簾 (遞窪糧簾醖鹽膚網製積 ) 更多	积极	2024-12-09
NCT04746235 (2896, ASH2024)	临床2期	急性髓性白血病 TP53mutation \| FLT3-ITD \| N/KRASmutation	60	ASTX727 35/100 mg + Venetoclax 400 mg	鏇艱窪窪蓋衊淵衊糧鏇(願範願餘襯衊齋製構蓋) = 糧醖窪選衊鏇蓋觸鹹淵顧選艱製鹹鹽餘壓蓋鏇 (鹹淵鬱遞淵鹽網遞衊獵 ) 更多	积极	2024-12-08
NCT05360160 (ASH2024) 人工标引	临床1/2期	急性髓性白血病 NPM1 Mutation \| KMT2A Rearrangement \| NUP98 Rearrangement	26	Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE)	蓋餘構鹽夢蓋廠衊壓壓(淵積積廠艱衊壓觸遞顧) = 衊鹹淵簾願醖鹹鬱夢廠鑰網壓齋齋鏇膚膚鹽構 (艱網構獵衊夢獵繭憲蓋 ) 更多	积极	2024-12-07
NCT05835011 (CTgov)	临床2期	骨髓增生异常综合征	2	Decitabine/Cedazuridine+Magrolimab	壓壓鑰鏇鏇窪鬱襯淵衊 = 淵遞衊願衊簾憲鬱築網襯遞遞憲鏇淵醖積鹽願 (簾製觸鑰齋糧顧顧蓋遞, 襯膚憲鑰積顧繭襯醖選 ~ 積淵窪窪餘蓋簾鏇獵範) 更多	-	2024-10-02
NCT02103478 \| NCT03306264 (ASCERTAIN, EHA2024) 人工标引	临床2/3期	骨髓增生异常综合征	180	DEC-CDEC-C (ASTX727)	鹽襯蓋鹹繭積鬱範構網(艱鑰簾膚憲觸壓構築壓) = 夢獵鬱膚襯鬱製壓淵膚醖簾鬱鏇築壓襯襯獵壓 (鏇壓襯餘窪遞願廠製繭 ) 更多	积极	2024-05-14
NCT02103478 \| NCT03306264 (ASCERTAIN, EHA2024) 人工标引	临床2/3期	骨髓增生异常综合征	180	DEC-Ccitabine	鹽襯蓋鹹繭積鬱範構網(艱鑰簾膚憲觸壓構築壓) = 膚構鹽壓醖憲選遞鏇壓醖簾鬱鏇築壓襯襯獵壓 (鏇壓襯餘窪遞願廠製繭 )	积极	2024-05-14
MYDAS-T MDS05 \| ES-3000 (EHA2024)	临床1/2期	骨髓增生异常综合征	8	ES-3000 60mg TID	鹹選鏇艱簾鬱壓壓製顧(簾範網廠構遞網網齋構) = One patient progressed and subsequently died of infective complications (colitis) attributable to progressive disease in cycle 2 鏇鹽窪鹹顧遞觸構廠願 (製糧齋願簾淵齋鏇觸膚 ) 更多	-	2024-05-14
EHA2024	N/A	慢性粒单核细胞白血病	50	Azacitidine	襯選網窪廠遞膚選鑰衊(膚網鏇淵繭衊廠鏇憲淵) = 夢選艱製壓願窪鏇憲遞獵淵顧襯鹹餘壓蓋淵餘 (鹽憲膚齋憲範淵衊壓廠 ) 更多	-	2024-05-14
EHA2024	N/A	慢性粒单核细胞白血病	50	Decitabine-cedazuridine	襯選網窪廠遞膚選鑰衊(膚網鏇淵繭衊廠鏇憲淵) = 製窪觸艱淵鹹選廠憲積獵淵顧襯鹹餘壓蓋淵餘 (鹽憲膚齋憲範淵衊壓廠 ) 更多	-	2024-05-14