Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML

This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia chromosome or BCR-ABL positive chronic myelogenous leukemia, who are resistant or intolerant to imatinib mesylate (Gleevec).

Sex

All

Minimum age

18 Years

Maximum age

90 Years

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

* Subjects with Philadelphia chromosome positive (Ph+) (or BCR/ABL+) chronic phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate.
* Men and women, 18 years or older
* Adequate hepatic function
* Adequate renal function
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Subjects who are eligible and willing to undergo transplantation during the screening period
* A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
* Uncontrolled or significant cardiovascular disease
* Medications that increase bleeding risk
* Medications that change heart rhythms
* Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
* History of significant bleeding disorder unrelated to CML
* Concurrent incurable malignancy other than CML
* Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

• BACKGROUNDPorkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer. 2010 Jan 15;116(2):377-86. doi: 10.1002/cncr.24734. PMID 19924787
• BACKGROUNDMuller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24. PMID 19779040
• BACKGROUNDShah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12. doi: 10.1200/JCO.2007.14.9260. Epub 2008 Jun 9. PMID 18541900
• DERIVEDShah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J, Mohamed H, Healey D, Kantarjian H, Hochhaus A, Saglio G. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016 Sep;91(9):869-74. doi: 10.1002/ajh.24423. Epub 2016 Jun 20. PMID 27192969
• DERIVEDShah NP, Guilhot F, Cortes JE, Schiffer CA, le Coutre P, Brummendorf TH, Kantarjian HM, Hochhaus A, Rousselot P, Mohamed H, Healey D, Cunningham M, Saglio G. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014 Apr 10;123(15):2317-24. doi: 10.1182/blood-2013-10-532341. Epub 2014 Feb 25. PMID 24569263