A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in the Treatment of Adult Newly Diagnosed Early Precursor T-cell Acute Lymphoblastic Leukemia (ETP-ALL)

ETP-ALL is a subtype of T-cell acute lymphoblastic leukemia (T-ALL) with poor outcomes and prognosis. Effective induction therapy is crucial in improving the treatment effect. Based on our laboratory research and clinical practice, the venetoclax plus HAG regimen shows promising efficacy in treating ETP-ALL. Therefore, we plan to conduct a prospective, multicenter Phase III clinical study to evaluate the efficacy of the venetoclax plus HAG regimen in treating newly diagnosed ETP-ALL patients.

开始日期2024-04-01

申办/合作机构

The First Affiliated Hospital, Zhejiang University School of Medicine

NCT06221683 / Recruiting临床2期IIT

A Multicenter Clinical Study of Molecular Subtyping Combined With MRD-driven Remission Induction Regimen in Children and Adolescents With AML: A Phase II Cohort Study (GMCAII)

The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.

开始日期2024-03-01

申办/合作机构-

NCT05906914 / Recruiting临床2期

A Monocenter Prospective Single Arm Study of Cladribine Plus Homoharringtonine and Cytarabine Regimen (CHA) for Induced Therapy in Adults de Novo Acute Myeloid Leukemia (Non-M3)

The goal of this clinical trial is to evaluate the response and safety of Cladribine plus Homoharringtonine and Cytarabine regimen (CHA) protocol in de novo acute myeloid leukemia with age <60y. This is a prospective, single-armed mono-center based investigator-initiated trial. About 30 patients who meet the enrollment criteria with be treated with CHA as induction chemotherapy. The complete response rate, survival rate, recurrence rate, and treatment-related mortality with be observed.

开始日期2023-06-29

申办/合作机构

The First Affiliated Hospital, Zhejiang University School of Medicine

100 项与高三尖杉酯碱相关的临床结果

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100 项与高三尖杉酯碱相关的转化医学

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100 项与高三尖杉酯碱相关的专利（医药）

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项与高三尖杉酯碱相关的文献（医药）

2024-03-01·Acta pharmacologica Sinica

Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML

Article

作者: Liu, Han ; Dai, Yu-Ting ; Lei, Yi-Chen ; Liu, Ping ; Dai, Bing ; Chen, Xin-Jie ; Wang, Ji-Yue ; Chen, Bing ; Wang, Kan-Kan ; Li, Miao-Hui ; Jiang, Lu

Understanding the molecular pathogenesis of acute myeloid leukemia (AML) with well-defined genomic abnormalities has facilitated the development of targeted therapeutics. Patients with t(8;21) AML frequently harbor a fusion gene RUNX1-RUNX1T1 and KIT mutations as "secondary hit", making the disease one of the ideal models for exploring targeted treatment options in AML. In this study we investigated the combination therapy of agents targeting RUNX1-RUNX1T1 and KIT in the treatment of t(8;21) AML with KIT mutations. We showed that the combination of eriocalyxin B (EriB) and homoharringtonine (HHT) exerted synergistic therapeutic effects by dual inhibition of RUNX1-RUNX1T1 and KIT proteins in Kasumi-1 and SKNO-1 cells in vitro. In Kasumi-1 cells, the combination of EriB and HHT could perturb the RUNX1-RUNX1T1-responsible transcriptional network by destabilizing RUNX1-RUNX1T1 transcription factor complex (AETFC), forcing RUNX1-RUNX1T1 leaving from the chromatin, triggering cell cycle arrest and apoptosis. Meanwhile, EriB combined with HHT activated JNK signaling, resulting in the eventual degradation of RUNX1-RUNX1T1 by caspase-3. In addition, HHT and EriB inhibited NF-κB pathway through blocking p65 nuclear translocation in two different manners, to synergistically interfere with the transcription of KIT. In mice co-expressing RUNX1-RUNX1T1 and KIT^N822K, co-administration of EriB and HHT significantly prolonged survival of the mice by targeting CD34⁺CD38^- leukemic cells. The synergistic effects of the two drugs were also observed in bone marrow mononuclear cells (BMMCs) of t(8;21) AML patients. Collectively, this study reveals the synergistic mechanism of the combination regimen of EriB and HHT in t(8;21) AML, providing new insight into optimizing targeted treatment of AML.

2024-02-01·Journal of internal medicine

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3‐ITD: A multicenter phase 2 study

Article

作者: Wang, Yu ; Guo, Ziwen ; Zhang, Xiong ; Zhang, Hongyu ; Yu, Sijian ; Xiao, Jie ; Deng, Lan ; Xu, Na ; Liu, Qifa ; Liu, Qiong ; Liang, Xinquan ; Xuan, Li ; Shao, Ruoyang ; Dai, Min ; Zhao, Weihua ; Fan, Zhiping ; Yu, Guopan ; Zhang, Yu ; Du, Xin ; Lin, Dongjun ; Sun, Zhiqiang ; Lin, Ren ; Jin, Hua ; Huang, Fen ; Shi, Pengcheng ; Jiang, Xuejie

Abstract:

Background:

Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3‐internal tandem duplication (FLT3‐ITD) respond infrequently to salvage chemotherapy.

Objective:

To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population.

Methods:

This multicenter, single‐arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3‐ITD (aged 18–65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival.

Results:

Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31–57). CRc was 76.5% with ORR of 82.4%. At a median follow‐up of 17.7 months (IQR, 8.7–24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8‐NR) and event‐free survival was 11.4 months (95% CI, 5.6‐NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment‐related death occurred in two (3.9%) patients.

Conclusions:

The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3‐ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored.

Trial registration:

Clinical Trials Registry: NCT04424147

2024-02-01·Journal of biological rhythms

The Molecular Circadian Clock Is a Target of Anti-cancer Translation Inhibitors

Article

作者: Vinod, Manjula ; Gheeraert, Céline ; Berthier, Alexandre ; Staels, Bart ; Lefebvre, Philippe ; Eeckhoute, Jérôme ; Johanns, Manuel

Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration.

项与高三尖杉酯碱相关的新闻（医药）

2024-06-21

·BioSpace

Tectonic Completes Reverse Merger With Avrobio, Starts Trading on Nasdaq

Pictured: Nasdaq headquarters in New York City/iStock, JHVEPhoto Tectonic Therapeutic completed its reverse merger with Avrobio on Thursday, with plans to begin trading Friday on the Nasdaq under the ticker symbol TECX. The biotech also completed a $130 million private placement with a group of new and existing investors, concurrent with the reverse merger. The fresh capital plus cash on hand are expected to fund operations into mid-2027. “We believe we are strongly positioned to enter the public markets at this time, with a solid financial foundation, investor syndicate and leadership team, and with several potential catalysts over the next two years, setting the stage for meaningful value creation,” Tectonic CEO Alise Reicin said in a statement. Tectonic is developing GPCR-targeted therapeutic proteins for indications currently underserved by small molecule treatments. Its GEODe platform is intended to overcome the common challenges of GPCR-targeted biologics. The new company will take Tectonic’s lead program into a Phase II trial for a population of Pulmonary Hypertension patients in the second half of this year. TX45 is a fusion molecule that activates the GPCR target of the hormone relaxin. Relaxin had been considered a “wonder drug” for cardiovascular benefits, but previous studies have failed to produce those benefits in the clinic. Tectonic believes its protein engineering has potential to overcome those limitations to develop relaxin as a therapeutic. A clinical candidate is being selected for its second program to treat hereditary hemorrhagic telangiectasia (HHT) later this year, with studies commencing by the end of 2025 or start of 2026. HHT is the second most common genetic bleeding disorder. The program has first-in-indication potential. Prior to the merger, Avrobio was focused on curative Hematopoietic stem cells (HSC) gene therapies. After announcing positive Phase I/II results in May 2023, the company sold its HSC gene therapy program for cystinosis to Novartis in June of that year for $87.5 million. In January 2024, Avrobio announced it was halting program development and exploring strategic alternatives including a merger. As part of the closing of the merger with Tectonic, Avrobio exercised a 1 for 12 reverse stock split of its common stock. With the closing of the merger, prior Avrobio stockholders own approximately 24.8% on a diluted basis and prior Tectonic stockholders hold approximately 75.2% of the combined company's outstanding common stock on a diluted basis. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

并购基因疗法临床2期

2024-04-03

·FierceBiotech

Diagonal launches with $128M and a platform slanted toward agonist antibodies

Diagonal Therapeutics is building a pipeline of antibody agonists rather than receptor blockers. Diagonal Therapeutics is taking shape, launching with $128 million and backed by the likes of BVF Partners, Atlas Venture and RA Capital to develop a pipeline of antibody agonists. The company will use this significant financial firepower to accelerate development of its pipeline of four assets. Two of these candidates are more advanced, including a lead asset targeting the inherited bleeding disorder hereditary hemorrhagic telangiectasia (HHT) and a runner-up designed to treat pulmonary arterial hypertension (PAH). Unlike conventional antibody development, Diagonal is working on candidates that activate broken signaling pathways rather than inhibit them. The HHT asset, for example, reignites a receptor in the TGF-β superfamily, with preclinical models showing that the agonist antibodies “prevent and reverse the formation of pathological vascular malformations,” the company said in a release. The $128 million will pay for at least a proof-of-concept study for the HHT program, the company noted in its announcement, though a full cash runway was not specified. Diagonal is led by CEO Alex Lugovskoy, Ph.D., an entrepreneur-in-residence at Atlas who’s had previous C-suite stints at Dragonfly Therapeutics and Morphic Therapeutic. Diagonal's platform is the byproduct of computational and scientific advancements made in the last five to 10 years, Lugovskoy told Fierce Biotech. “I think more and more people will start using those types of approaches to all kinds of antibody engineering techniques, which is a blend of experimental and computational,” the CEO said in an interview. Diagonal’s stated PAH ambitions come days after Merck & Co.’s much-hyped Winrevair (sotatercept) received FDA approval for the condition, resetting the competitive landscape. Lugovskoy conceded that unlike HHT, which lacks treatment options, Winrevair is a “significant advance” for PAH patients. But he said that because the drug acts as an activin receptor ligand trap rather than a fix for genetic mutations, the worst case scenario for Diagonal is that its own candidate—if approved—is synergistic on the marketplace. “I do not see us directly competing with sotatercept because what we are doing is promoting missing signaling, whereas [Merck is] inhibiting excessive activin signaling,” Lugovskoy said. Diagonal has a good sense of Winrevair's capabilities, with Acceleron's former vice president of biology, Patrick Andre, Ph.D., now Diagonal's chief scientific officer. Merck got hold of Winrevair when it acquired Acceleron for $11.5 billion in 2021. Equipped with new cash, Lugovskoy expects Diagonal will grow its head count in the single digits, with most of the new jobs centered on building clinical capabilities.

并购上市批准抗体药物偶联物

2024-03-27

·CPHI制药在线

一文了解伴FLT3突变急性髓系白血病，3款新型FLT3抑制剂带来新希望

关注并星标CPHI制药在线FLT3是急性髓系白血病（AML）中经常出现的突变基因。当AML患者的FLT3基因发生突变时，他们的疾病预后往往较差，且更容易复发。因此，及时识别FLT3基因的突变情况，并选择恰当的治疗策略，对AML患者的治疗效果具有重要意义。 Fms样酪氨酸激酶3（FLT3）在细胞信号传递路径中起着关键作用，作为一种受体酪氨酸激酶。实际上，AML中出现的最常见的基因突变，其中一个就是在FLT3。这一基因的突变在成人AML患者中约占了30%的比例。其突变形式主要有两种，即FLT3的内部串联重复序列（FLT3-ITD）和酪氨酸激酶结构域（FLT3-TKD）突变。在这些突变中，FLT3-ITD是最常见的，其在AML中的检出率达到了25% [1]。 FLT3突变急性髓系白血病（AML）患者的临床特点通常为年纪偏大、白细胞与血小板计数偏高，以及骨髓原始细胞比例偏高。尽管这些患者的缓解率较低，且治疗后容易复发，但常规化疗的复发率也相对较高，且往往伴随着其他基因突变。特别值得关注的是，一些最常见的共存基因突变包括NPM1、DNMT3A、WT1、TET2、RAS、RUNX1以及PTPN11。对于FLT3-TKD突变，其预后仍然存在争议；相比之下，FLT3-ITD突变具有较强的异质性，预后受其等位基因比率（AR）、插入位点、ITD长度、核型以及其他伴随基因突变如NPM1、DNMT3A、WT1、RUNX1的影响而有所不同。值得关注的是，与NPM1突变同时出现的FLT3-ITD AML的预后相对较好，然而，当与IDH1/2、TET2、DNMT3A、WT1突变同时出现，或者同时合并NPM1和DNMT3A突变时，FLT3-ITD AML的预后则较差。随着对FLT3突变AML发病机制的深入了解、新的检测技术的出现以及FLT3抑制剂的广泛应用，其预后已得到显著改善。因此，根据欧洲白血病网（ELN 2022）的最新指南，所有FLT3-ITD AML现已被归类为中危。 FLT3抑制剂属于酪氨酸激酶抑制剂，通过竞争激酶活性区域的ATP结合位点抑制FLT3蛋白发生磷酸化，进而抑制相关下游生长信号通路（PI3K/Akt、Ras/MAPK和STAT5等）发挥治疗作用。根据FLT3抑制剂与FLT3结合的程度，可将FLT3抑制剂分为第一代和第二代抑制剂和新型FLT3抑制剂。一代FLT3抑制剂索拉非尼索拉非尼是一种能够同时抑制RAF、VEGFR、KIT和FLT3等多个靶点的小分子药物。南方医科大学血液病研究院的刘启发教授领导的研究团队进行了一项临床研究[7]，他们评估了将索拉非尼与维奈克拉、阿扎胞苷和高三尖杉酯碱（简称VAH方案）联合使用，在患有FLT3-ITD阳性的复发/难治性急性髓系白血病（AML）患者中的治疗效果和患者的耐受程度。研究数据表明，患者接受这一治疗方案后的总缓解率高达82.4%。中位随访期为17.7个月，研究尚未观察到中位复合完全缓解（CRc）的持续时间。这些患者的总生存期（OS）平均为18.1个月，无事件生存期（EFS）平均为11.4个月。在接受治疗的患者中，出现3-4级不良事件（AE）的情况包括中性粒细胞减少症、血小板减少导致的贫血、发热性中性粒细胞减少症、肺炎和脓毒症等。其中，有2名患者因治疗相关原因不幸去世。米哚妥林欧洲药品管理局（EMA）和美国食品药品监督管理局（FDA）共同批准了米哚妥林与标准化疗相结合，作为针对FLT3突变成年急性髓系白血病（AML）患者的首选治疗策略。除此之外，对于经历过异基因造血干细胞移植（allo-HSCT）的患者，米哚妥林在维持治疗方面也表现出显著效果，它不仅能够优化患者的预后，而且其安全性也得到了充分验证[8]。这些进展为患有急性髓系白血病（AML）的患者提供了新的治疗选择和更好的康复机会。二代FLT3抑制剂吉瑞替尼（Gilteritinib） 2018年11月28日，美国食品药品监督管理局（FDA）正式批准吉瑞替尼作为治疗FLT3突变型复发或难治性急性髓系白血病（AML）成人患者的药物。随后，在2021年，吉瑞替尼获得中国批准并上市，用以治疗患有复发或难治性FLT3突变型AML的患者[9]。由中国医学科学院血液病医院王健祥教授率领的团队，联合多个国家包括中国、俄罗斯、新加坡、泰国和马来西亚等，开展了一项名为COMMODORE的III期开放、多中心临床试验，对比了吉瑞替尼与挽救性化疗（SC）在治疗FLT3突变复发难治AML患者上的疗效[10]。研究显示，吉瑞替尼组（包含116名患者）的完全缓解（CR）率达到了16.4%，这一数据超过了挽救性化疗（SC）组（包含118名患者，CR率为10.2%）。此外，吉瑞替尼组患者的1年中位总生存期（mOS）也显著长于挽救性化疗（SC）组，分别为9个月和4.7个月（P=0.001 26）。这一研究成果再次确立了吉瑞替尼在针对FLT3突变复发难治AML治疗上的显著优势。奎扎替尼（Quizartinib） 2023年7月20日，美国食品药品监督管理局（FDA）正式批准了奎扎替尼联合标准阿糖胞苷、蒽环类药物的诱导治疗与阿糖胞苷巩固治疗，以及在巩固化疗后单独使用奎扎替尼作为维持治疗，这一治疗方案针对的是新诊断的FLT3-ITD阳性急性髓系白血病（AML）成年患者。这项医疗进展意味着对白血病治疗的一个重要突破，可以为这些患者提供更好的治疗效果和生存率。 QuANTUM-First（NCT02668653）试验是一项双盲随机、安慰剂对照的研究，共纳入了539名新诊断的FLT3-ITD阳性急性髓系白血病患者。通过对奎扎替尼组与安慰剂组之间的对比分析，结果显示，奎扎替尼组在总生存期（OS）上具有显著的统计学意义改善[风险比（HR）0.78，95%置信区间（CI）0.62-0.98，两组比较p=0.0324]。这一数据进一步证明了奎扎替尼在治疗FLT3-ITD阳性急性髓系白血病患者中的疗效和安全性，为这一病症的治疗提供了新的选择。 Crenolanib Richard M. Stone教授的研究团队，隶属于美国丹娜法伯癌症研究所，进行了一项关键性的II期研究[7]，旨在评估在新发现的FLT3突变急性髓系白血病（AML）病患中结合使用Crenolanib的治疗成效。该研究涉及了44名患者（男性占22名），他们的中位数年龄是57岁（年龄范围：19-75岁）。结果显示，总体复合完全缓解（CRc）率高达73%（32/44）。特别是在经过两个周期的治疗后，总CRc率跃升至86%（38/44）。年轻患者的总体缓解率表现尤为突出，达到了90%，且其MRD阴性率高达89%。相较之下，尽管年长患者的总体缓解率为80%，但他们的MRD阴性率相对较低，为45%。此外，值得注意的是，超过70%的年轻患者在接受治疗后的三年时间里仍然存活。这项研究的结果为FLT3突变急性髓系白血病的治疗提供了新的方向，尤其是对于那些年轻的患者，Crenolanib联合治疗方案展现出了显著的效果。新型FLT3抑制剂 Tuspetinib Tuspetinib，这是一种新兴的可口服FLT3抑制剂，凭借其强大的能力，被公认为一种高效的髓系激酶抑制药物。它的作用机制在于能够抑制导致AML细胞增殖异常的多种激酶，这当中就包括了SYK、FLT3、JAK1/2、RSK1/2、突变型KIT和TAK1-TAB1激酶等。一项涉及I/II期的研究[13]对Tuspetinib单独使用（TUS）和与维奈克拉联合使用（VEN/TUS）治疗复发性或难治性AML（R/R AML）的安全性和疗效进行了评估，并确定了II期推荐剂量（RP2D）。该研究的结果表明，Tuspetinib单药治疗的安全性较高，总体完全缓解/完全缓解伴部分血液学恢复（CR/CRh）的比率为36%。对于FLT3突变型AML患者，这一比率高达50%，而对于FLT3野生型AML患者，这一比率则为25%。这些结果为Tuspetinib在AML治疗中的潜在应用提供了重要的临床依据。 EmavusertibEmavusertib作为一种创新型的FLT3抑制剂，其独特之处在于可以口服使用，为治疗提供了便利。它能够精确地针对IRAK4和FLT3进行作用，表现出令人满意且可管理的安全性。目前，TakeAim Leukemia试验正在深入研究Emavusertib在治疗复发/难治性急性髓性白血病（R/R AML）和高危骨髓增生异常综合征（HR-MDS）方面的安全性、临床疗效以及潜在的生物标志物，为未来的治疗策略提供更为坚实的科学依据。 EP0042 EP0042是一款口服型的药物，它能够有效抑制FLT3和Aurora激酶。研究表明，Aurora激酶在急性髓系白血病（AML）的发病过程中扮演着关键角色，并与FLT3抑制剂耐药性的产生密切相关。因此，EP0042通过同时针对FLT3和Aurora激酶，有望克服对选择性FLT3抑制所产生的获得性耐药性。为了探索EP0042的最佳给药方案，一项I/IIa期研究采用了标准的3+3剂量递增设计，并纳入了复发/难治性AML或骨髓增生异常综合征（MDS）的患者进行临床试验[15]。总结 FLT3抑制剂的研发成功，为那些罹患FLT3突变急性髓性白血病（AML）的患者提供了全新治疗策略。在临床应用中，目前已有一线和二线的FLT3抑制剂可供选用。不仅如此，新型的FLT3抑制剂，如Tuspetinib、Emavusertib和EP0042，也正在接受临床试验的检验，其初步成果显示出了良好的治疗潜力。随着对FLT3突变机制的深入研究以及药物研发的持续进步，我们有理由期待更多高效、精准的靶向治疗药物的出现。这些药物的问世，将为AML患者带来更加显著的治疗效果，帮助他们更好地战胜疾病。参考文献： [1] 邱林，马军. 急性髓系白血病靶向治疗研究进展[J]. 白血病·淋巴瘤， 2022,31(4):197-203. DOI：10.3760/cma.j.cn115356-20220210-00033 . [2] Yu S, Zhang Y, Yu G, Wang Y, Shao R, Du X, et al. Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/ relapsed acute myeloid leukemia with FLT3ITD: A multicenter phase 2 study. J Intern Med.2023;00:1-13. [3] 袁伟，张世忠，主鸿鹄. FLT3抑制剂治疗急性髓系白血病患者研究进展[J].浙江大学学报:医学版, 2022, 51(4):507-514. [4]https://www.fda.gov/drugs/fda-approves-gilteritinib-relapsed-or-refractory-acute-myeloid-leukemia-aml-flt3-mutation [5] Wang JX ， Jiang B ， Li J ，et al. Gilteritinib versus salvage chemotherapy for relapsed/refractory FLT3-mutated acute myeloid leukemia：a phase 3，randomized，multicenter，open-label trial in Asia[J]. Blood， 2021，138Suppl 1：695. doi: 10.1182/blood-2021-145436 .[6] https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia[7] Eunice S. Wang, et al. 2022ASCO.Abstract#7007.[8] Naval Daver, et al. Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy As Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). 2023 ASH. Abstract #162.[9] Eric S Winer, et al. Preliminary Safety and Efficacy of Emavusertib (CA-4948) in Acute Myeloid Leukemia Patients with FLT3 Mutation. 2023 ASH. Abstract #2924.[10] David Taussig, et al. EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Results from an Ongoing Phase I/IIa Dose-Finding/Dose Optimization Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia. 2023 ASH. Abstract #4285. [6] Zhao J , Agarwal S , Ahmad H ,et al.A review of FLT3 inhibitors in acute myeloid leukemia[J].Blood reviews, 2021:100905. [7] 张钰, 邵若洋, 刘启发. FLT3突变急性髓系白血病的全程管理[J].临床血液学杂志,2023,36(5):303-308 [8] DöhnerH, WeiAH, Appelbaum FR, et al. Diagnosis ·and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN [J].Blood,2022,140(12):1345-1377. [9] WANG Z, CAI J, CHENG J, et al. FLT3 inhibitors in acute myeloid leukemia: challenges and recent developments in overcoming resistance[J]. J Med Chem, 2021, 64(6): 2878-2900. [10] 袁伟，张世忠，主鸿鹄. FLT3抑制剂治疗急性髓系白血病患者研究进展[J].浙江大学学报:医学版, 2022, 51(4):507-514. [11] TALLMAN M S, WANG E S, ALTMAN J K, et al. Acute myeloid leukemia, version 3.2019, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2019, 17(6): 721-749. [12] LEVIS M. Midostaurin approved for FLT3-mutated AML[J]. Blood, 2017, 129(26): 3403-3406. [13] SERVE H, KRUG U, WAGNER R, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial[J]. J Clin Oncol, 2013, 31(25): 3110-3118. [14] YILMAZ M, KANTARJIAN H M, MUFTUOGLU M, et al. Quizartinib with decitabine +/- venetoclax is highly active in patients (pts) with FLT3-ITD mutated (mut) acute myeloid leukemia (AML): clinical report and signaling cytof profiling from a phase Ⅰb/Ⅱ trial[J]. Blood, 2020, 136(Supplement 1): 19-20. [15] PERL A E, MARTINELLI G, CORTES J E, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML[J]. N Engl J Med, 2019, 381(18): 1728-1740. [16] WANG R, LI Y, GONG P, et al. Arsenic/trioxide and sorafenib induce synthetic lethality of FLT3-ITD acute myeloid leukemia cells[J]. Mol Cancer Ther, 2018,17(9): 1871-1880. [17] YILMAZ M, KANTARJIAN H, SHORT N J, et al. Hypomethylating agent and venetoclax with FLT3 inhibitor "triplet" therapy in older/unfit patients with FLT3 mutated AML[J]. Blood Cancer J, 2022, 12(5): 77.【智药研习社近期课程预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床结果

100 项与高三尖杉酯碱相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08956	高三尖杉酯碱	L01XX40	DB04865

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
加速期慢性骨髄性白血病	美国	Teva Pharmaceuticals International GmbH	2012-10-26
骨髓增生异常综合征	中国	哈药集团三精制药有限公司初创企业	-
费城染色体阳性慢性粒细胞白血病	中国	哈药集团三精制药有限公司初创企业	-
真性红细胞增多症	中国	哈药集团三精制药有限公司初创企业	-

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床3期	中国	苏州大学附属第一医院	2023-03-01
急性红细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性巨核细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
伴有 11q23 异常的急性髓系白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性髓细胞白血病伴多系发育不良	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性髓单核细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
成人急性单核细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
伴del(5q)成人急性髓系白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
复发性急性髓细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性转化期慢性粒细胞性白血病	临床2期	美国	ChemGenex Pharmaceuticals Pty Ltd.	2005-10-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASH2023	N/A	复发性急性髓细胞白血病	321	VEN plus AZA and HHT (VAH)	鏇繭鹹鑰壓鏇艱膚齋構(窪鏇鬱鑰鏇繭壓廠積蓋) = 衊願鏇膚餘願齋夢鏇齋醖顧鬱齋壓遞鏇獵齋鹽 (淵選鏇築願築製網製繭 ) 更多	-	2023-12-11
ASH2023	N/A	复发性急性髓细胞白血病	321	VEN plus AZA (VA)	鏇繭鹹鑰壓鏇艱膚齋構(窪鏇鬱鑰鏇繭壓廠積蓋) = 糧鏇餘構範鑰窪餘艱鏇醖顧鬱齋壓遞鏇獵齋鹽 (淵選鏇築願築製網製繭 ) 更多	-	2023-12-11
ChiCTR-OIC-16007764 (RJ-AML 2016, ASH2023)	临床3期	急性髓性白血病	747	Idarubicin and Cytarabine	積襯壓網衊範顧醖鏇糧(襯鑰願鹽夢獵製壓遞醖) = 製鏇鏇齋壓膚蓋膚鹹簾遞淵築築網積鹽顧構築 (積獵遞廠構衊鬱襯鏇鬱 )	-	2023-12-11
ChiCTR-OIC-16007764 (RJ-AML 2016, ASH2023)	临床3期	急性髓性白血病	747	Idarubicin and Cytarabine + Homoharringtonine	積襯壓網衊範顧醖鏇糧(襯鑰願鹽夢獵製壓遞醖) = 鹹鹹齋憲夢窪選網網網遞淵築築網積鹽顧構築 (積獵遞廠構衊鬱襯鏇鬱 )	-	2023-12-11
ASH2023	N/A	成人急性髓性白血病	25	Venetoclax	積鹹積願製蓋構鏇觸餘(衊廠積鏇鏇顧鏇獵淵膚) = The most frequent hematological adverse events were Grade 3 to 4 anemia, thrombocytopenia, and neutropenia during the induction treatment and occurred in all patients (25/25 100%) 繭廠夢積簾淵艱壓獵糧 (齋淵夢壓襯壓網壓網簾 ) 更多	-	2023-12-10
ChiCTR2100048208 (EHA2023)	临床3期	急性髓性白血病	-	HAV regimen (HHT and cytarabine combined with venetoclax)	構簾糧壓憲網簾衊選鑰(築範艱夢鹽膚餘夢積繭) = 14.7% (5/34) 襯遞壓觸艱繭鏇廠醖廠 (積繭顧糧壓糧鏇衊糧構 ) 更多	-	2023-06-08
ChiCTR2000029841 (EHA2023)	临床2期	急性髓性白血病	21	Bortezomib, Homoharringtonine, and Cytarabine (BHA)	餘獵廠糧積蓋獵襯夢鑰(願積餘鹹鏇壓積獵繭餘) = 14.3% 艱網遞構鑰壓醖窪鏇構 (淵醖壓醖醖窪襯淵網構 ) 更多	积极	2023-06-08
EHA2023	N/A	复发性急性髓细胞白血病	32	Venetoclax+Azacitidine+Homoharringtonine+Cytarabine	膚製鏇鹹壓憲鬱選築繭(積窪觸範淵壓鑰醖範齋) = 顧廠膚獵構壓範襯齋蓋襯夢鬱憲襯糧廠窪壓簾 (憲艱築獵憲積鬱糧壓壓 ) 更多	-	2023-06-08
RJ-AML 2014 (Pubmed \| Am J Hematol)	临床2期	急性髓性白血病	151	Idarubicin and cytarabine with homoharringtonine	構築築積齋願顧鹹鏇壓(衊蓋齋夢衊簾鏇鹹網鏇) = 齋膚衊餘繭鬱鹽顧蓋選夢餘築廠願窪築淵糧壓 (壓蓋衊網衊廠築鹹廠構 )	-	2021-10-23
NCT02440568 (CTgov)	临床1/2期	急性髓性白血病	22	Omacetaxine+Cytarabine+Idarubicin (Patients With Newly Diagnosed AML, Cohort 1)	鹽窪簾顧網齋齋餘積鹽(範夢齋繭鏇壓鏇範夢鏇) = 衊醖觸艱艱鬱顧築壓壓餘衊鏇餘網淵觸製簾繭 (網獵範製鏇膚餘餘艱艱, 選積鹹積餘獵選壓廠膚 ~ 獵淵鹹艱製鹽憲鬱襯製) 更多	-	2021-07-06
NCT02440568 (CTgov)	临床1/2期	急性髓性白血病	22	Omacetaxine+Cytarabine+Idarubicin (Patients With Newly Diagnosed AML, Cohort 2)	鹽窪簾顧網齋齋餘積鹽(範夢齋繭鏇壓鏇範夢鏇) = 窪鏇網網顧製獵鹹範觸餘衊鏇餘網淵觸製簾繭 (網獵範製鏇膚餘餘艱艱, 衊衊觸選窪範網醖膚選 ~ 襯憲顧淵積鏇膚壓觸繭) 更多	-	2021-07-06
NCT02078960 (CTgov)	临床1/2期	费城染色体阳性慢性粒细胞白血病 \| 加速期慢性骨髄性白血病	10	omacetaxine (Cohort 1)	繭窪築廠襯觸鑰觸廠鏇(襯遞積製襯製鹽積觸簾) = 齋壓觸衊艱鹹築窪膚餘範願淵築網衊鏇製網繭 (觸鬱範鏇網鹽醖鏇觸網, 淵鏇窪齋襯齋構淵網鹹 ~ 窪顧積鹹選糧膚範範顧) 更多	-	2019-01-14
NCT02078960 (CTgov)	临床1/2期	费城染色体阳性慢性粒细胞白血病 \| 加速期慢性骨髄性白血病	10	omacetaxine (Cohort 2)	繭窪築廠襯觸鑰觸廠鏇(襯遞積製襯製鹽積觸簾) = 窪艱齋簾選淵夢蓋繭範範願淵築網衊鏇製網繭 (觸鬱範鏇網鹽醖鏇觸網, 選鬱糧範窪膚窪繭艱範 ~ 鹹蓋窪壓艱壓蓋鏇鏇築) 更多	-	2019-01-14
NCT02159872 (Pubmed \| Am J Hematol) 人工标引	临床2期	慢性粒单核细胞白血病 \| 骨髓增生异常综合征	42	omacetaxine mepesuccinate	遞顧網簾觸糧餘簾鑰鑰(願簾鹽廠窪鏇廠憲窪遞) = 遞積網糧築構蓋積醖淵壓淵顧淵鹹廠衊網夢餘 (積鹹夢願糧壓願築壓齋 ) 更多	积极	2019-01-01