Improving the Outcome of Patients with Chronic Myeloid Leukemia Through Medi

通过医疗改善慢性粒细胞白血病患者的预后

• 批准号: 8332846
• 负责人: Jorge E Cortes
• 金额: $ 133.02万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8332846
• 关键词: 2-tyrosine; Blast Phase; Cells; Chronic Myeloid Leukemia; Chronic-Phase Myeloid Leukemia; Clinical; Cytogenetics; Dasatinib; Data; Decitabine; Disease; Disease remission; Event; Failure; Goals; Grant; Imatinib; Immunotherapy; Interferons; JAK2 gene; Lead; Malignant - descriptor; Modality; Molecular; Newly Diagnosed; Outcome; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Phenotype; Polymerase; Progression-Free Survivals; Proteinase 3; Randomized; Refractory; Relapse; Residual Neoplasm; Residual Tumors; Resistance development; Staging; Testing; Treatment Efficacy; Tyrosine Kinase Inhibitor; Vaccines; base; cell mediated lymphocytolysis test; immunoregulation; improved; inhibitor/antagonist; response; success

The main objective of this project is to identify improved therapeufic opfions for pafients with CML. Imafinib is standard therapy for CML, but neariy 20% of patients never achieve complete cytogenetic remission, and most have residual disease by polymerase chain reacfion, and 10-15% of those who achieve remission eventually progress. More potent tyrosine kinase inhibitors (TKI) such as dasatinib and nilotinib have significant clinical activity after imatinib failure. The first aim is to determine whether dasatinib or nilotinib may improve the molecular response, and event-free and progression-free survival of patients with newly diagnosed chronic phase CML. Pafients will be treated in one of two parallel studies with the primary objective to improve the molecular response rate at 12 months. The second aim is to invesfigate whether immunotherapy, in the form of PRI vaccine, can improve molecular responses of patients with minimal residual disease on imatinib therapy. Because Interferon may improve the expression of proteinase 3 from which PRI is derived, patients with this phenotype will be randomized to receive PRI and imatinib, with or without interferon. The primary objective is to improve the molecular response with PRI vaccine. Based on data originated through this grant suggesting activation of JAK2 in Bcr-Abl-posifive cells, the third aim is to invesfigate whether JAK2 inhibition may have clinical activity in CML pafients refractory to TKI. We will conduct a phase 2 trial of INCB18424, a JAK2 inhibitor, in patients who failed at least 2 TKI. The long-term plan is to use this agent in combination with TKI. The fourth aim deals with the problem of patients with blast phase, a group with dismal outcome with available therapy. Dasatinib induces high response rates but most patients eventually relapse. Increased methylafion is associated with progression in CML. We will thus treat patients with blast phase CML with decitabine, a hypomethylating agent, and dasafinib to determine whether this combinafion may improve the rate and durability of responses in blast phase CML. Overall, this project may lead to improved long-term outcome for patients with all phases ofthe disease and get us closer to complete eradication of CML.

该项目的主要目的是确定改善CML Pafients的治疗方法。 imafinib是 CML的标准疗法，但近20％的患者从未实现完全的细胞遗传学缓解，并且 大多数通过聚合酶链重新出现残留疾病，而10-15％的人有10-15％ 最终进步。更有效的酪氨酸激酶抑制剂（TKI），例如dasatinib和nilotinib具有 伊马替尼失败后的重要临床活性。第一个目的是确定dasatinib或nilotinib是否可以 改善新的患者的分子反应以及无事件和无事件的生存 诊断为慢性期CML。在两项平行研究之一中，将对养护物进行治疗 在12个月时提高分子反应率的目的。第二个目的是提出是否 免疫疗法以PRI疫苗的形式可以改善最少患者的分子反应 伊马替尼治疗的残留疾病。因为干扰素可能会改善蛋白酶3的表达 衍生哪个PRI，具有该表型的患者将随机分配以接受PRI和伊马替尼，或 没有干扰素。主要目的是改善PRI疫苗的分子反应。基于 通过这笔赠款提出的数据表明，在BCR-ABL促成细胞中激活JAK2，第三个目的是 Invesfate JAK2抑制是否可能在CML适应于TKI的CML能量中具有临床活性。我们将 对至少2个TKI失败的患者进行了INCB18424（JAK2抑制剂）INCB18424的2期试验。长期 计划是将此代理与TKI结合使用。第四个目标涉及爆炸患者的问题 阶段，一组可用治疗的惨淡结果。达沙替尼诱导高应答率，但大多数 患者最终复发。甲基二氮与CML的进展有关。因此，我们将对待 爆炸期CML的患者，甲基化剂和达萨非尼的患者是否确定是否是否 该组合可以提高爆炸相CML中响应的速率和耐用性。总体而言，这个项目 可能会改善疾病各个阶段的患者的长期结局，并使我们更接近 完全根除CML。