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    • 7. 发明申请
    • METHOD OF OPTIMIZING THE TREATMENT OF PHILADELPHIA-POSITIVE LEUKEMIA WITH ABL TYROSINE KINASE INHIBITORS
    • ABL酪氨酸激酶抑制剂优化治疗费城阳性白血病的方法
    • WO2008036792A2
    • 2008-03-27
    • PCT/US2007/078978
    • 2007-09-20
    • NOVARTIS AGGATHMANN, InsaMAHON, Francois-XavierMOLIMARD, MathieuPICARD, StéphaneWANG, Yanfeng
    • GATHMANN, InsaMAHON, Francois-XavierMOLIMARD, MathieuPICARD, StéphaneWANG, Yanfeng
    • A61K49/00A61P35/02A61K31/00A61K31/506
    • A61K31/506A61K31/00G01N33/49G01N2800/52
    • The present invention provides a method of treating Philadelphia positive (Ph+) leukemia, such as Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML), in a human patient population comprising the steps of (a) administering a predetermined fixed amount of a Bcr-Abl tyrosine kinase inhibitor, such as Imatinib, or a pharmaceutically acceptable salt thereof to human patients suffering from a Ph+ leukemia, (b) collecting at least one blood sample from said patients, (c) determining the plasma trough level (Cmin) of the Bcr-Abl tyrosine kinase inhibitor or of a metabolite thereof as well as the MMR rates, (d) assessing a discrimination potential of trough plasma concentrations for MMR and identifying a Cmin threshold for optimal sensitivity and specificity and (e) adjusting the dose of the inhibitor of the Bcr-Abl tyrosine kinase or a pharmaceutically acceptable salt thereof applied to the individual patients from said patient population and, optionally, future patients suffering from a Ph+ leukemia in a manner that a Cmin is achieved in each single patient equal to or higher than the Cmin threshold obtained under step (d).
    • 本发明提供了治疗患者群中费城阳性(Ph +)白血病(例如费城染色体阳性急性淋巴细胞白血病(Ph + ALL)或慢性粒细胞白血病(CML))的方法, (a)将预定固定量的Bcr-Abl酪氨酸激酶抑制剂如伊马替尼或其药学上可接受的盐给予患有Ph +白血病的人类患者,(b)从所述患者中收集至少一种血液样品 ,(c)确定Bcr-Abl酪氨酸激酶抑制剂或其代谢物的血浆谷值水平(Cmin)以及MMR率,(d)评估MMR的谷底血浆浓度的辨别潜力并鉴定Cmin阈值 以获得最佳灵敏度和特异性,和(e)调节应用于所述患者的个体患者的Bcr-Abl酪氨酸激酶或其药学上可接受的盐的抑制剂的剂量 nt群体以及任选患有Ph +白血病的未来患者,其方式为每个单个患者的Cmin达到等于或高于步骤(d)中获得的Cmin阈值。
    • 9. 发明申请
    • METHOD OF OPTIMIZING THE TREATMENT OF PHILADELPHIA-POSITIVE LEUKEMIA WITH IMATINIB MESYLATE
    • 利用肌醇六磷酸酯优化治疗菲律宾阳性淋巴细胞的方法
    • WO2010065433A1
    • 2010-06-10
    • PCT/US2009/066045
    • 2009-11-30
    • NOVARTIS AGMEDVET SCIENCE PTY. LTD.WANG, YanfengKALEBIC, TheaHUGHES, Timothy PeterWHITE, Deborah
    • WANG, YanfengKALEBIC, TheaHUGHES, Timothy PeterWHITE, Deborah
    • A61K31/506A61K35/02
    • A61K31/506
    • The present invention relates to a method of treating Philadelphia-positive leukemia (Ph+ leukemia), in a particular chronic myeloid leukemia (CML), in a human patient population. More specifically, the present invention pertains to a method of treating Ph+ leukemia, such as CML or Ph+ ALL, in a human patient suffering from Ph+ leukemia comprising the steps of (a) administering a predetermined fixed amount of Imatinib as a free base or in the form of a pharmaceutically acceptable salt thereof to the human patient, (b) collecting at least one blood sample from the patient, e.g. within the first 12 months of treatment, (c) determining the plasma trough level (Cmin) of Imatinib, (d) determining the OCT-1 Activity in the blood sample, and (e) adjusting the dose of Imatinib applied to the individual patient in a manner that an Imatinib Cmin value is achieved in the patient of at least 800 ng/mL, if in step (c) an Imatinib Cmin value of less than 800 ng/mL is found and in step (d) an OCT-1 Activity is found below 6.0 to 10.0 ng/200,000 cells..
    • 本发明涉及在人类患者群体中治疗特定慢性骨髓性白血病(CML)中的费城阳性白血病(Ph +白血病)的方法。 更具体地,本发明涉及在患有Ph +白血病的人类患者中治疗Ph +白血病(例如CML或Ph + ALL)的方法,包括以下步骤:(a)施用预定的固定量的伊马替尼作为游离碱或 其药学上可接受的盐的形式提供给人类患者,(b)从患者收集至少一种血液样品, 在治疗的头12个月内,(c)确定伊马替尼的血浆谷值(Cmin),(d)确定血液样品中的OCT-1活性,和(e)调整施用于个体患者的伊马替尼剂量 如果在步骤(c)中发现伊马替尼Cmin值小于800ng / mL,并且在步骤(d)中OCT-1 活动发现低于6.0至10.0ng / 20万个细胞。