Prospective randomized multicenter phase III trial of decitabine and Venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy

地西他滨和维奈托克联合全反式维甲酸或安慰剂治疗不适合诱导化疗的急性髓系白血病患者的前瞻性随机多中心 III 期试验

• 批准号: 367848349
• 负责人: Professor Dr. Michael Lübbert, Ph.D.
• 金额: --
• 依托单位: Klinik für Innere Medizin I - Hämatologie, Onkologie und Stammzelltransplantation
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/367848349?language=en
• 关键词: Prospective; randomized; multicenter; phase; III

Acute myeloid leukemia (AML) is a type of cancer that occurs predominantly in the elderly, with age of diagnosis often 70+ years. Until recently, therapeutic options for these patients were very limited, since intensive chemotherapy, standard for younger AML patients, often led to unacceptable toxicities, and frequently was not as effective as in younger patients. Better tolerated, mild AML therapy is provided by the epigenetically active medicines Decitabine and Azacitidine. These very closely related drugs are given on an outpatient basis, are well tolerated also by elderly patients with comorbidities, and thought to act by reprogramming of the leukemia cells, thus probably by different mechanisms of action than conventional chemotherapy. To enhance the efficacy of this epigenetic therapy - by itself not leading to cure of AML - numerous drug combinations have been clinically tested during the last years. Through a collaboration within a trial network of physicians from different German University Hospitals, we could demonstrate in the multicenter clinical trial DECIDER (registered under NCT00867672) that Decitabine infusions in combination with a vitamin A derivative (ATRA capsules) led to an increase in overall survival of elderly AML patients (median age 76 years) compared to treatment with Decitabine alone. Within the planned successor study (DECIDER-2) our primary objective is to confirm the extension of patient survival with ATRA add-on compared to treatment without ATRA add-on. Half of the patients will receive ATRA capsules in addition to Decitabine, the other half will receive placebo capsules instead of ATRA in combination with Decitabine (double-blind randomized study). All patients will receive, in addition, a third drug (Venetoclax capsules) with the aim to accelerate the programmed cell death in the AML cells. The study is planned to accrue 250 patients at more than 30 German study sites. While the most important study question is to find out whether patients receiving ATRA will live longer than patients receiving placebo (in combination with the other two drugs), a second important objective is the measurement of quality of life before and during this AML therapy. Here we hope that patients benefiting from the treatment will also enjoy an improvement of their quality of life. In accompanying laboratory studies, the mechanism of action of this novel therapy shall be studied using bone marrow and blood cells of the patients, in order to be able to make better predictions about which patient will profit most from such chemotherapy-free treatment.

急性髓性白血病（AML）是一种主要发生于老年人的癌症，诊断年龄通常为70岁以上。直到最近，这些患者的治疗选择非常有限，因为强化化疗，年轻AML患者的标准，往往导致不可接受的毒性，而且往往不如年轻患者有效。表观遗传活性药物地西他滨和阿扎胞苷提供了更好的耐受性，轻度AML治疗。这些非常密切相关的药物在门诊病人中使用，对有合并症的老年患者也有良好的耐受性，并且被认为是通过白血病细胞的重新编程起作用，因此可能与传统化疗的作用机制不同。为了提高这种表观遗传疗法的疗效（它本身不能治愈AML），在过去几年里，许多药物组合已经进行了临床试验。通过与来自不同德国大学医院的医生的试验网络的合作，我们可以在多中心临床试验DECIDER（注册号NCT00867672）中证明，与单独使用地西他滨治疗相比，地西他滨输注联合维生素a衍生物（ATRA胶囊）可提高老年AML患者的总生存率（中位年龄76岁）。在计划的后续研究（ider -2）中，我们的主要目标是确认与不加ATRA治疗相比，加ATRA治疗延长了患者的生存期。一半的患者将接受ATRA胶囊和地西他滨，另一半患者将接受安慰剂胶囊代替ATRA联合地西他滨（双盲随机研究）。此外，所有患者将接受第三种药物（Venetoclax胶囊），旨在加速AML细胞的程序性细胞死亡。该研究计划在德国30多个研究地点收集250名患者。虽然最重要的研究问题是发现接受ATRA的患者是否会比接受安慰剂（与其他两种药物联合）的患者活得更长，但第二个重要的目标是测量AML治疗前和治疗期间的生活质量。在这里，我们希望从治疗中受益的患者也能享受到生活质量的改善。在相应的实验室研究中，将利用患者的骨髓和血细胞来研究这种新疗法的作用机制，以便能够更好地预测哪些患者将从这种无化疗治疗中获益最多。