A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.
Identifieur interne : 003564 ( PubMed/Corpus ); précédent : 003563; suivant : 003565A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.
Auteurs : J F Seymour ; D W Kim ; E. Rubin ; A. Haregewoin ; J. Clark ; P. Watson ; T. Hughes ; I. Dufva ; J L Jimenez ; F-X Mahon ; P. Rousselot ; J. Cortes ; G. Martinelli ; C. Papayannidis ; A. Nagler ; F J GilesSource :
- Blood cancer journal [ 2044-5385 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Aged, Amino Acid Substitution, Female, Fusion Proteins, bcr-abl (genetics), Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy), Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics), Male, Middle Aged, Mutation, Missense, Philadelphia Chromosome, Piperazines (administration & dosage), Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy), Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics), Protein Kinase Inhibitors (administration & dosage).
- MESH :
- chemical , administration & dosage : Piperazines, Protein Kinase Inhibitors.
- chemical , genetics : Fusion Proteins, bcr-abl.
- drug therapy : Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- genetics : Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- Adult, Aged, Amino Acid Substitution, Female, Humans, Male, Middle Aged, Mutation, Missense, Philadelphia Chromosome.
Abstract
Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty-two patients (CP, n=15; AP, n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved major cytogenetic response; 6% achieved unconfirmed complete or partial response; 39% had no response. Two patients (CP CML) achieved complete hematologic response. No patients with advanced CML or Ph+ ALL achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected toxicities were observed. These data will assist in the development of future aurora kinase inhibitors and in the selection of appropriate target patient populations.
DOI: 10.1038/bcj.2014.60
PubMed: 25127392
Links to Exploration step
pubmed:25127392Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.</title><author><name sortKey="Seymour, J F" sort="Seymour, J F" uniqKey="Seymour J" first="J F" last="Seymour">J F Seymour</name><affiliation><nlm:affiliation>Haematology Service Division of Cancer Medicine, Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, University of Melbourne, Parkville, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, D W" sort="Kim, D W" uniqKey="Kim D" first="D W" last="Kim">D W Kim</name><affiliation><nlm:affiliation>St. Mary's Hospital, Seoul, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Rubin, E" sort="Rubin, E" uniqKey="Rubin E" first="E" last="Rubin">E. Rubin</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Haregewoin, A" sort="Haregewoin, A" uniqKey="Haregewoin A" first="A" last="Haregewoin">A. Haregewoin</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Clark, J" sort="Clark, J" uniqKey="Clark J" first="J" last="Clark">J. Clark</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Watson, P" sort="Watson, P" uniqKey="Watson P" first="P" last="Watson">P. Watson</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hughes, T" sort="Hughes, T" uniqKey="Hughes T" first="T" last="Hughes">T. Hughes</name><affiliation><nlm:affiliation>Haematology, SA Pathology, Adelaide, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Dufva, I" sort="Dufva, I" uniqKey="Dufva I" first="I" last="Dufva">I. Dufva</name><affiliation><nlm:affiliation>Herlev University Hospital, Herlev, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Jimenez, J L" sort="Jimenez, J L" uniqKey="Jimenez J" first="J L" last="Jimenez">J L Jimenez</name><affiliation><nlm:affiliation>Hospital Universitario Ramon y Cajal, Madrid, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Mahon, F X" sort="Mahon, F X" uniqKey="Mahon F" first="F-X" last="Mahon">F-X Mahon</name><affiliation><nlm:affiliation>Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rousselot, P" sort="Rousselot, P" uniqKey="Rousselot P" first="P" last="Rousselot">P. Rousselot</name><affiliation><nlm:affiliation>Hopital de Versailles, Université Versailles Saint Quentin en, Yvelines, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cortes, J" sort="Cortes, J" uniqKey="Cortes J" first="J" last="Cortes">J. Cortes</name><affiliation><nlm:affiliation>MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Martinelli, G" sort="Martinelli, G" uniqKey="Martinelli G" first="G" last="Martinelli">G. Martinelli</name><affiliation><nlm:affiliation>University of Bologna, Bologna, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Papayannidis, C" sort="Papayannidis, C" uniqKey="Papayannidis C" first="C" last="Papayannidis">C. Papayannidis</name><affiliation><nlm:affiliation>University of Bologna, Bologna, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Nagler, A" sort="Nagler, A" uniqKey="Nagler A" first="A" last="Nagler">A. Nagler</name><affiliation><nlm:affiliation>Chaim Sheba Medical Center, Tel Hashomer, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Giles, F J" sort="Giles, F J" uniqKey="Giles F" first="F J" last="Giles">F J Giles</name><affiliation><nlm:affiliation>Northwestern Medicine Developmental Therapeutics Institute, Chicago, IL, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25127392</idno><idno type="pmid">25127392</idno><idno type="doi">10.1038/bcj.2014.60</idno><idno type="wicri:Area/PubMed/Corpus">003564</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003564</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.</title><author><name sortKey="Seymour, J F" sort="Seymour, J F" uniqKey="Seymour J" first="J F" last="Seymour">J F Seymour</name><affiliation><nlm:affiliation>Haematology Service Division of Cancer Medicine, Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, University of Melbourne, Parkville, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, D W" sort="Kim, D W" uniqKey="Kim D" first="D W" last="Kim">D W Kim</name><affiliation><nlm:affiliation>St. Mary's Hospital, Seoul, South Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Rubin, E" sort="Rubin, E" uniqKey="Rubin E" first="E" last="Rubin">E. Rubin</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Haregewoin, A" sort="Haregewoin, A" uniqKey="Haregewoin A" first="A" last="Haregewoin">A. Haregewoin</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Clark, J" sort="Clark, J" uniqKey="Clark J" first="J" last="Clark">J. Clark</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Watson, P" sort="Watson, P" uniqKey="Watson P" first="P" last="Watson">P. Watson</name><affiliation><nlm:affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hughes, T" sort="Hughes, T" uniqKey="Hughes T" first="T" last="Hughes">T. Hughes</name><affiliation><nlm:affiliation>Haematology, SA Pathology, Adelaide, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Dufva, I" sort="Dufva, I" uniqKey="Dufva I" first="I" last="Dufva">I. Dufva</name><affiliation><nlm:affiliation>Herlev University Hospital, Herlev, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Jimenez, J L" sort="Jimenez, J L" uniqKey="Jimenez J" first="J L" last="Jimenez">J L Jimenez</name><affiliation><nlm:affiliation>Hospital Universitario Ramon y Cajal, Madrid, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Mahon, F X" sort="Mahon, F X" uniqKey="Mahon F" first="F-X" last="Mahon">F-X Mahon</name><affiliation><nlm:affiliation>Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rousselot, P" sort="Rousselot, P" uniqKey="Rousselot P" first="P" last="Rousselot">P. Rousselot</name><affiliation><nlm:affiliation>Hopital de Versailles, Université Versailles Saint Quentin en, Yvelines, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cortes, J" sort="Cortes, J" uniqKey="Cortes J" first="J" last="Cortes">J. Cortes</name><affiliation><nlm:affiliation>MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Martinelli, G" sort="Martinelli, G" uniqKey="Martinelli G" first="G" last="Martinelli">G. Martinelli</name><affiliation><nlm:affiliation>University of Bologna, Bologna, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Papayannidis, C" sort="Papayannidis, C" uniqKey="Papayannidis C" first="C" last="Papayannidis">C. Papayannidis</name><affiliation><nlm:affiliation>University of Bologna, Bologna, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Nagler, A" sort="Nagler, A" uniqKey="Nagler A" first="A" last="Nagler">A. Nagler</name><affiliation><nlm:affiliation>Chaim Sheba Medical Center, Tel Hashomer, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Giles, F J" sort="Giles, F J" uniqKey="Giles F" first="F J" last="Giles">F J Giles</name><affiliation><nlm:affiliation>Northwestern Medicine Developmental Therapeutics Institute, Chicago, IL, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Blood cancer journal</title><idno type="ISSN">2044-5385</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Female</term><term>Fusion Proteins, bcr-abl (genetics)</term><term>Humans</term><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)</term><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation, Missense</term><term>Philadelphia Chromosome</term><term>Piperazines (administration & dosage)</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics)</term><term>Protein Kinase Inhibitors (administration & dosage)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Piperazines</term><term>Protein Kinase Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fusion Proteins, bcr-abl</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation, Missense</term><term>Philadelphia Chromosome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty-two patients (CP, n=15; AP, n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved major cytogenetic response; 6% achieved unconfirmed complete or partial response; 39% had no response. Two patients (CP CML) achieved complete hematologic response. No patients with advanced CML or Ph+ ALL achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected toxicities were observed. These data will assist in the development of future aurora kinase inhibitors and in the selection of appropriate target patient populations.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25127392</PMID><DateCreated><Year>2014</Year><Month>08</Month><Day>16</Day></DateCreated><DateCompleted><Year>2015</Year><Month>09</Month><Day>16</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>15</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Print">2044-5385</ISSN><JournalIssue CitedMedium="Print"><Volume>4</Volume><PubDate><Year>2014</Year><Month>Aug</Month><Day>15</Day></PubDate></JournalIssue><Title>Blood cancer journal</Title><ISOAbbreviation>Blood Cancer J</ISOAbbreviation></Journal><ArticleTitle>A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia.</ArticleTitle><Pagination><MedlinePgn>e238</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/bcj.2014.60</ELocationID><Abstract><AbstractText>Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty-two patients (CP, n=15; AP, n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved major cytogenetic response; 6% achieved unconfirmed complete or partial response; 39% had no response. Two patients (CP CML) achieved complete hematologic response. No patients with advanced CML or Ph+ ALL achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected toxicities were observed. These data will assist in the development of future aurora kinase inhibitors and in the selection of appropriate target patient populations.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Seymour</LastName><ForeName>J F</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>Haematology Service Division of Cancer Medicine, Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, University of Melbourne, Parkville, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>D W</ForeName><Initials>DW</Initials><AffiliationInfo><Affiliation>St. Mary's Hospital, Seoul, South Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rubin</LastName><ForeName>E</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haregewoin</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clark</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watson</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Merck & Co., Inc, Whitehouse Station, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hughes</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Haematology, SA Pathology, Adelaide, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dufva</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Herlev University Hospital, Herlev, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jimenez</LastName><ForeName>J L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Hospital Universitario Ramon y Cajal, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mahon</LastName><ForeName>F-X</ForeName><Initials>FX</Initials><AffiliationInfo><Affiliation>Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rousselot</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Hopital de Versailles, Université Versailles Saint Quentin en, Yvelines, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cortes</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>MD Anderson Cancer Center, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martinelli</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>University of Bologna, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Papayannidis</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>University of Bologna, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagler</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Chaim Sheba Medical Center, Tel Hashomer, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>F J</ForeName><Initials>FJ</Initials><AffiliationInfo><Affiliation>Northwestern Medicine Developmental Therapeutics Institute, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 CA016672</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D017427">Clinical Trial, Phase II</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>08</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Blood Cancer J</MedlineTA><NlmUniqueID>101568469</NlmUniqueID><ISSNLinking>2044-5385</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010879">Piperazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>639089-54-6</RegistryNumber><NameOfSubstance UI="C484810">VX680</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="D016044">Fusion Proteins, bcr-abl</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Blood. 2003 Jul 1;102(1):276-83</RefSource><PMID Version="1">12623848</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2013 Nov 7;369(19):1783-96</RefSource><PMID Version="1">24180494</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Hematol. 2004;83 Suppl 1:S65-6</RefSource><PMID Version="1">15124676</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 1973 Jun 1;243(5405):290-3</RefSource><PMID Version="1">4126434</PMID></CommentsCorrections><CommentsCorrections 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Kinase Inhibitors</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4219463</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>06</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>06</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>8</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>8</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>9</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25127392</ArticleId><ArticleId IdType="pii">bcj201460</ArticleId><ArticleId 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