Advanced phase Philadelphia chromosome-positive myeloid disease—consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia—is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases.

中文翻译：

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地西他滨、维奈托克和普纳替尼治疗晚期慢性粒细胞白血病和费城染色体阳性急性髓性白血病：一项单臂、单中心 2 期试验


晚期费城染色体阳性髓系疾病（包括髓母细胞期和加速期的慢性髓系白血病，以及费城染色体阳性急性髓系白血病）与不良结局相关。尽管先前的研究表明化疗和 BCR：：ABL1 酪氨酸激酶抑制剂联合治疗有益，但最佳方案尚不确定，对这组罕见疾病的前瞻性研究很少。临床前和回顾性临床数据表明 BCL-2 抑制剂 venetoclax 和 BCR：：ABL1 酪氨酸激酶抑制剂之间可能存在协同作用。因此，我们旨在设计一项研究，以评估地西他滨、维奈托克和第三代 BCR：：ABL1 酪氨酸激酶抑制剂普纳替尼的新型组合在晚期费城染色体阳性髓系疾病中的安全性和活性。