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The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. <jats:italic>Methods<\/jats:italic> Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25\u201390\u00a0mg for 14 or 21 consecutive days plus 14 or 7\u00a0days\u2019 rest, respectively, or MLN8237 ECT, at a starting dose of 40\u00a0mg\/day once-daily (QD) for 14\u00a0days plus 14\u00a0days\u2019 rest, all in 28-day\u00a0cycles. Subsequent cohorts received MLN8237 ECT 30\u201350\u00a0mg twice-daily (BID) for 7\u00a0days plus 14\u00a0days\u2019 rest in 21-day\u00a0cycles. <jats:italic>Results<\/jats:italic> Fifty-eight patients were enrolled (PIC <jats:italic>n<\/jats:italic>\u2009=\u200928, ECT <jats:italic>n<\/jats:italic>\u2009=\u200930). The most frequent grade \u22653 drug-related toxicities were neutropenia (45\u00a0%), thrombocytopenia (28\u00a0%), anemia (19\u00a0%), and leukopenia (19\u00a0%). The maximum tolerated dose on the ECT 7-day schedule was 50\u00a0mg BID. The terminal half-life of MLN8237 was approximately 19\u00a0h. Six (13\u00a0%) patients achieved partial responses and 13 (28\u00a0%) stable disease. <jats:italic>Conclusion<\/jats:italic> The recommended phase II dose of MLN8237 ECT is 50\u00a0mg BID for 7\u00a0days in 21-day\u00a0cycles, which is currently being evaluated as a single agent in phase II\/III trials in patients with peripheral T-cell lymphoma.<\/jats:p>","DOI":"10.1007\/s10637-013-0050-9","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T04:56:22Z","timestamp":1387428982000},"page":"489-499","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Phase I study of MLN8237\u2014investigational Aurora A kinase inhibitor\u2014in relapsed\/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia"],"prefix":"10.1007","volume":"32","author":[{"given":"Kevin R.","family":"Kelly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Goy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus G.","family":"Berdeja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig B.","family":"Reeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.","family":"McDonagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Danaee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Ecsedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifeng","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ely","family":"Benaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaminathan","family":"Padmanabhan Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,12,20]]},"reference":[{"key":"50_CR1","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1242\/jcs.013136","volume":"120","author":"AR Barr","year":"2007","unstructured":"Barr AR, Gergely F (2007) Aurora-A: the maker and breaker of spindle poles. 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