Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias

Summary

This is an open-label, continuous daily dosing, two-part safety and efficacy study of SKI-606 (bosutinib) in Philadelphia chromosome positive leukemias (Ph+). Part 1 is a dose-escalation study in chronic phase Chronic Myelogenous Leukemia (CML) subjects to establish the maximum tolerated dose (MTD) in this subject population. Part 2 has begun after the completion of Part 1 and after a dose has been established for the compound in chronic phase subjects. Part 2 is a study of the the efficacy of 500mg daily oral SKI-606 (bosutinib) in patients with all phases of Ph+ CML and Ph+ Acute Lymphocytic Leukemia (ALL). The protocol will test the hypotheses that oral daily dosing of bosutinib at 500 mg will attain (1) Major Cytogenetic Response (MCyR) in chronic phase CML patients and (2) Overall Hematological Response (OHR) in advanced leukemia patients. Each phase of the disease will be evaluated as a separate cohort.

Timeline

Start

2006-01-18

Primary completion

2009-09-25

Completion

2015-08-06

Publications

• Takahashi N, Cortes JE, Sakaida E, Ishizawa K, Ono T, Doki N, Matsumura I, Garcia-Gutierrez V, Rosti G, Ono C, Ohkura M, Tanetsugu Y, Viqueira A, Brummendorf TH. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol. 2022 Jun;115(6):838-851. doi: 10.1007/s12185-022-03314-y. Epub 2022 Mar 2.
• Kota V, Brummendorf TH, Gambacorti-Passerini C, Lipton JH, Kim DW, An F, Leip E, Crescenzo RJ, Ferdinand R, Cortes JE. Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosome-positive leukemias. Leuk Res. 2021 Dec;111:106690. doi: 10.1016/j.leukres.2021.106690. Epub 2021 Aug 21.
• Gambacorti-Passerini C, Cortes JE, Lipton JH, Kantarjian HM, Kim DW, Schafhausen P, Crescenzo R, Bardy-Bouxin N, Shapiro M, Noonan K, Leip E, DeAnnuntis L, Brummendorf TH, Khoury HJ. Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica. 2018 Aug;103(8):1298-1307. doi: 10.3324/haematol.2017.171249. Epub 2018 May 17.
• Kantarjian HM, Mamolo CM, Gambacorti-Passerini C, Cortes JE, Brummendorf TH, Su Y, Reisman AL, Shapiro M, Lipton JH. Long-term patient-reported outcomes from an open-label safety and efficacy study of bosutinib in Philadelphia chromosome-positive chronic myeloid leukemia patients resistant or intolerant to prior therapy. Cancer. 2018 Feb 1;124(3):587-595. doi: 10.1002/cncr.31082. Epub 2017 Oct 26.
• Cortes JE, Khoury HJ, Kantarjian HM, Lipton JH, Kim DW, Schafhausen P, Matczak E, Leip E, Noonan K, Brummendorf TH, Gambacorti-Passerini C. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016 Dec;91(12):1206-1214. doi: 10.1002/ajh.24536. Epub 2016 Sep 15.
• Whiteley J, Reisman A, Shapiro M, Cortes J, Cella D. Health-related quality of life during bosutinib (SKI-606) therapy in patients with advanced chronic myeloid leukemia after imatinib failure. Curr Med Res Opin. 2016 Aug;32(8):1325-34. doi: 10.1185/03007995.2016.1174108. Epub 2016 May 5.
• Hsyu PH, Mould DR, Abbas R, Amantea M. Population pharmacokinetic and pharmacodynamic analysis of bosutinib. Drug Metab Pharmacokinet. 2014;29(6):441-8. doi: 10.2133/dmpk.DMPK-13-RG-126. Epub 2014 Jun 10.
• Gambacorti-Passerini C, Brummendorf TH, Kim DW, Turkina AG, Masszi T, Assouline S, Durrant S, Kantarjian HM, Khoury HJ, Zaritskey A, Shen ZX, Jin J, Vellenga E, Pasquini R, Mathews V, Cervantes F, Besson N, Turnbull K, Leip E, Kelly V, Cortes JE. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up. Am J Hematol. 2014 Jul;89(7):732-42. doi: 10.1002/ajh.23728. Epub 2014 Apr 28.
• Kantarjian HM, Cortes JE, Kim DW, Khoury HJ, Brummendorf TH, Porkka K, Martinelli G, Durrant S, Leip E, Kelly V, Turnbull K, Besson N, Gambacorti-Passerini C. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood. 2014 Feb 27;123(9):1309-18. doi: 10.1182/blood-2013-07-513937. Epub 2013 Dec 17.
• Trask PC, Cella D, Powell C, Reisman A, Whiteley J, Kelly V. Health-related quality of life in chronic myeloid leukemia. Leuk Res. 2013 Jan;37(1):9-13. doi: 10.1016/j.leukres.2012.09.013. Epub 2012 Oct 29.
• Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brummendorf TH. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012 Apr 12;119(15):3403-12. doi: 10.1182/blood-2011-11-390120. Epub 2012 Feb 27.
• Trask PC, Cella D, Besson N, Kelly V, Masszi T, Kim DW. Health-related quality of life of bosutinib (SKI-606) in imatinib-resistant or imatinib-intolerant chronic phase chronic myeloid leukemia. Leuk Res. 2012 Apr;36(4):438-42. doi: 10.1016/j.leukres.2011.10.011. Epub 2011 Oct 28.
• Cortes JE, Kantarjian HM, Brummendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011 Oct 27;118(17):4567-76. doi: 10.1182/blood-2011-05-355594. Epub 2011 Aug 24.

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