{"id":"https://openalex.org/W2979620775","doi":"https://doi.org/10.1182/blood.v120.21.3627.3627","title":"A Phase I Trial of Escalating Dose of the Rapamycin Analog Everolimus in Combination with the Kinase Inhibitor Midostaurin in Patients (pts) with Relapsed, Refractory or Poor Prognosis Acute Myeloid Leukemia (AML)","display_name":"A Phase I Trial of Escalating Dose of the Rapamycin Analog Everolimus in Combination with the Kinase Inhibitor Midostaurin in Patients (pts) with Relapsed, Refractory or Poor Prognosis Acute Myeloid Leukemia (AML)","publication_year":2012,"publication_date":"2012-11-16","ids":{"openalex":"https://openalex.org/W2979620775","doi":"https://doi.org/10.1182/blood.v120.21.3627.3627","mag":"2979620775"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v120.21.3627.3627","doi":"https://doi.org/10.1182/blood.v120.21.3627.3627","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.3627.3627","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5071023119","display_name":"Richard Maury Stone","orcid":"https://orcid.org/0000-0002-7526-2633","observed_orcids":["https://orcid.org/0000-0002-7526-2633"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Richard M. Stone","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063553060","display_name":"Caitlin D. Driscoll","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Caitlin Driscoll","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051795460","display_name":"Ilene A Galinsky","orcid":"https://orcid.org/0000-0002-9158-5061","observed_orcids":["https://orcid.org/0000-0002-9158-5061"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ilene Galinsky","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047939331","display_name":"Martha Wadleigh","orcid":"https://orcid.org/0000-0002-8191-1708","observed_orcids":["https://orcid.org/0000-0002-8191-1708"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Martha Wadleigh","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090527595","display_name":"David P. Steensma","orcid":"https://orcid.org/0000-0001-5130-9284","observed_orcids":["https://orcid.org/0000-0001-5130-9284"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David P. Steensma","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052641327","display_name":"David Avigan","orcid":"https://orcid.org/0000-0003-4624-6017","observed_orcids":["https://orcid.org/0000-0003-4624-6017"]},"institutions":[{"id":"https://openalex.org/I1316535847","display_name":"Beth Israel Deaconess Medical Center","ror":"https://ror.org/04drvxt59","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316535847"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Avigan","raw_affiliation_strings":["Beth Israel Deaconess Medical Center, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Beth Israel Deaconess Medical Center, Boston, MA, USA,","institution_ids":["https://openalex.org/I1316535847"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009091754","display_name":"Philip C. Amrein","orcid":"https://orcid.org/0000-0001-7770-2623","observed_orcids":["https://orcid.org/0000-0001-7770-2623"]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Philip C. Amrein","raw_affiliation_strings":["Massachusetts General Hospital, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111898613","display_name":"Suiyang Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Suiyang Liu","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039503690","display_name":"James D. Griffin","orcid":"https://orcid.org/0000-0003-1823-7930","observed_orcids":["https://orcid.org/0000-0003-1823-7930"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James D. Griffin","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5107174458","display_name":"Steven L. McAfee","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Steven L. McAfee","raw_affiliation_strings":["Massachusetts General Hospital, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089274301","display_name":"Eyal C. Attar","orcid":"https://orcid.org/0000-0002-1959-8079","observed_orcids":["https://orcid.org/0000-0002-1959-8079"]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eyal C. Attar","raw_affiliation_strings":["Massachusetts General Hospital, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045583767","display_name":"Karen Kuhn Ballen","orcid":"https://orcid.org/0000-0003-1706-3975","observed_orcids":["https://orcid.org/0000-0003-1706-3975"]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karen K. Ballen","raw_affiliation_strings":["Massachusetts General Hospital, Boston, MA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, MA, USA","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101585265","display_name":"Edward Fox","orcid":"https://orcid.org/0000-0002-3740-651X","observed_orcids":["https://orcid.org/0000-0002-3740-651X"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Edward Fox","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5082924494","display_name":"Daniel J. DeAngelo","orcid":"https://orcid.org/0000-0001-7865-2306","observed_orcids":["https://orcid.org/0000-0001-7865-2306"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Daniel J. DeAngelo","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5047939331","https://openalex.org/A5063553060","https://openalex.org/A5082924494","https://openalex.org/A5101585265","https://openalex.org/A5107174458","https://openalex.org/A5111898613"],"corresponding_institution_ids":["https://openalex.org/I4210087915","https://openalex.org/I4210117453"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":4,"citation_normalized_percentile":{"value":0.42284921,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"120","issue":"21","first_page":"3627","last_page":"3627"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11559","display_name":"Retinoids in leukemia and cellular processes","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12582","display_name":"Flavonoids in Medical Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/inertial-measurement-unit","display_name":"inertial measurement unit","score":0.9980000257492065},{"id":"https://openalex.org/keywords/midostaurin","display_name":"midostaurin","score":1.0},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.8989999890327454},{"id":"https://openalex.org/keywords/flt3-inhibitors","display_name":"FLT3 inhibitors","score":0.7020000219345093},{"id":"https://openalex.org/keywords/mtor-inhibitors","display_name":"mTOR inhibitors","score":0.843999981880188},{"id":"https://openalex.org/keywords/relapsed-refractory-aml","display_name":"relapsed/refractory AML","score":0.7829999923706055},{"id":"https://openalex.org/keywords/flt3-itd-mutation","display_name":"FLT3-ITD","score":0.8259999752044678},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.6940000057220459},{"id":"https://openalex.org/keywords/dose-escalation","display_name":"dose escalation","score":0.6230000257492065},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.6790000200271606},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.6110000014305115},{"id":"https://openalex.org/keywords/drug-toxicity","display_name":"drug toxicity","score":0.5619999766349792},{"id":"https://openalex.org/keywords/newly-diagnosed-aml","display_name":"newly diagnosed AML","score":0.5410000085830688}],"concepts":[{"id":"https://openalex.org/C2779699572","wikidata":"https://www.wikidata.org/wiki/Q421052","display_name":"Everolimus","level":2,"score":0.8992021083831787},{"id":"https://openalex.org/C2776481607","wikidata":"https://www.wikidata.org/wiki/Q6842945","display_name":"Midostaurin","level":3,"score":0.7773364782333374},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7190105319023132},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.577925980091095},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.5363795757293701},{"id":"https://openalex.org/C142424586","wikidata":"https://www.wikidata.org/wiki/Q7307572","display_name":"Refractory (planetary science)","level":2,"score":0.4260398745536804},{"id":"https://openalex.org/C2777063308","wikidata":"https://www.wikidata.org/wiki/Q1435822","display_name":"Neutropenia","level":3,"score":0.4250623285770416},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.36752474308013916},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.3598238229751587},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3384953439235687},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.3186114430427551},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.24330919981002808},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.08761760592460632},{"id":"https://openalex.org/C87355193","wikidata":"https://www.wikidata.org/wiki/Q411","display_name":"Astrobiology","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v120.21.3627.3627","doi":"https://doi.org/10.1182/blood.v120.21.3627.3627","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.3627.3627","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Clinical Trial","id":"https://openalex.org/study-designs/clinical-trial"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2080059445","https://openalex.org/W2889128568","https://openalex.org/W3012417840","https://openalex.org/W2891931626","https://openalex.org/W2771914151","https://openalex.org/W2530437175","https://openalex.org/W4243773276","https://openalex.org/W2603461724","https://openalex.org/W1744167954","https://openalex.org/W1993300766"],"abstract_inverted_index":{"Abstract":[0,1],"3627":[2],"Background:":[3],"In":[4,163,452,591],"pts":[5,168,234,245,312,340,374,390,410,421,465,529,551,569,572,578,594,632],"with":[6,13,46,103,171,249,255,267,547,718],"mutant":[7,82,516],"FLT3":[8,44,77,83,153,276,280,517],"AML":[9,258],"single":[10,655],"agent":[11,48,136],"studies":[12,644],"inhibitors":[14],"of":[15,24,95,116,134,159,174,201,214,243,310,319,336,346,366,388,549,588,601,625,685,709],"FLT3,":[16],"such":[17,67],"as":[18,68,111,157,357,653],"midostaurin,":[19],"yielded":[20],"a":[21,43,172,324,344,363,536,654,671],"high":[22],"rate":[23],"peripheral":[25,118,541],"blast":[26,119,537,545,561,626],"reduction":[27],"but":[28,702],"complete":[29],"and":[30,75,114,141,186,193,224,265,290,303,408,448,481,511,522,554,576,611,619,658,690,697],"partial":[31],"remissions":[32],"were":[33,169,217,235,246,294,353,411,437],"uncommon.":[34],"One":[35,515],"approach":[36],"to":[37,41,57,124,127,131,142,151,206,333,358,383,454,468,525,558],"overcome":[38],"resistance":[39],"is":[40,695,704],"combine":[42],"inhibitor":[45,78],"an":[47,370],"that":[49,64,97,487,640],"down-regulates":[50],"another":[51],"leukemogenic":[52],"pathway":[53],"including":[54,73,146,362,473],"those":[55],"downstream":[56],"activated":[58],"FLT3.":[59],"Preclinical":[60],"work":[61],"has":[62,698],"suggested":[63],"mTOR":[65],"inhibitors,":[66],"rapamycin":[69,711],"or":[70,542,563,628],"its":[71],"analogs":[72],"everolimus,":[74],"the":[76,90,149,212,238,315,329,337,376,414,433,455,460,592,675,707,710],"midostaurin":[79,109,175,646,686,719],"synergistically":[80],"kill":[81],"dependent":[84],"cell":[85],"lines.":[86],"Aims:":[87],"To":[88],"identify":[89],"maximum":[91],"tolerated":[92,113,375],"dose":[93,318,394],"(MTD)":[94],"everolimus":[96,187,202,215,316,416,462,691],"can":[98],"be":[99,359],"given":[100],"in":[101,139,148,155,296,300,305,422,459,491,567,630,642,674,700,714,731],"combination":[102,173,684],"50":[104,177,649],"mg":[105,178,219,226,321,378,385,418,650,688,693],"orally":[106],"twice":[107],"daily":[108],"(established":[110],"well":[112],"capable":[115],"decreasing":[117],"count":[120],"[Fischer":[121],"JCO":[122],"2010]),":[123],"determine":[125],"toxicities,":[126],"observe":[128,143],"anti-leukemic":[129],"effects,":[130],"measure":[132],"pharmacokinetics":[133],"each":[135],"when":[137],"administered":[138,189,647],"combination,":[140],"pharmacodynamic":[144,659],"effects":[145],"decrease":[147,673],"phospho-FLT3":[150],"total":[152,242,423],"ratio":[154],"blasts":[156,669],"evidence":[158],"enzyme":[160,680],"inhibition.":[161,681],"Methods:":[162],"this":[164,393,425],"phase":[165],"I":[166],"study":[167],"treated":[170,313,391,412],"at":[176,237,314,392,413,432,648,665],"po":[179,188,651],"BID":[180,652],"continuously":[181,194],"beginning":[182],"on":[183,190,524],"day":[184,191,196],"2":[185,304,548],"1":[192,266,279,299,309,342,533,555],"from":[195],"8":[197,571],"onward.":[198],"Dose":[199],"escalation":[200],"was":[203,286,331,565,635],"conducted":[204],"according":[205],"standard":[207,263],"3":[208,210,275,311,339,348,372,387,399,402,471,485,528,609],"+":[209],"schema;":[211],"doses":[213],"explored":[216],"5":[218,225,320,327,377,384,405,417,613],"QOD":[220,322,379,419],"(dose":[221,228],"level":[222,229,395],"1)":[223],"QD":[227],"2).":[230],"An":[231],"additional":[232,371],"15":[233,586,599],"enrolled":[236,247,341],"MTD.":[239],"Results:":[240],"A":[241],"29":[244],"(24":[248],"relapsed":[250,268],"and/or":[251,582],"refractory":[252],"AML,":[253,701],"4":[254,389],"newly":[256],"diagnosed":[257],"considered":[259],"inappropriate":[260],"candidates":[261],"for":[262,604],"therapy,":[264],"CMML;":[269],"11":[270],"FLTwt,":[271],"14":[272],"FLT3-ITD":[273,531],"positive,":[274,278,532],"D835Y":[277,518],"D835H":[281],"positive).":[282],"The":[283,350,427,623,683],"mean":[284],"age":[285],"66":[287],"(range":[288],"40\u201385)":[289],"ECOG":[291],"performance":[292],"statuses":[293],"0":[295],"6":[297,334,593],"pts,":[298,302],"16":[301],"7":[306],"pts.":[307],"After":[308,369],"starting":[317],"experienced":[323,343,396,535],"DLT":[325,345,397],"(grade":[326,398],"infection)":[328],"cohort":[330],"expanded":[332],"pts;":[335],"latter":[338],"grade":[347,401,404,470,608,612],"hypoxia.":[349],"eligibility":[351],"criteria":[352],"subsequently":[354],"amended":[355],"so":[356],"more":[360],"stringent,":[361],"DLCO":[364],"requirement":[365],"50%":[367],"predicted.":[368],"evaluable":[373],"dose,":[380],"we":[381],"escalated":[382],"QD;":[386],"hypoxia,":[400],"mucositis,":[403],"soft-tissue":[406],"infection),":[407],"subsequent":[409],"MTD,":[415],"(25":[420],"received":[424,583,596],"dose).":[426],"most":[428],"common":[429],"drug-related":[430,469],"toxicities":[431],"MTD":[434],"(any":[435],"grade)":[436],"fatigue":[438],"(40%),":[439],"nausea":[440,482],"(32%),":[441],"hypertriglyceridemia":[442],"(24%),":[443,445],"vomiting":[444],"hyperglycemia":[446],"(20%),":[447],"elevated":[449],"AST":[450],"(20%).":[451],"addition":[453,708],"pt":[456,519],"who":[457,595],"died":[458],"first":[461],"cohort,":[463],"5/25":[464],"discontinued":[466],"due":[467,557],"toxicity,":[472],"pneumonia":[474],"(1),":[475,480,496,500,502,505,508,510],"hypoxia":[476],"(2),":[477,498,615,618],"allergic":[478],"reaction":[479],"(1).":[483,622],"Grade":[484],"events":[486],"did":[488],"not":[489,636],"result":[490],"treatment":[492,605],"discontinuation":[493],"included":[494,607],"thrombocytopenia":[495],"dyspnea":[497],"hyponatremia":[499],"hypokalemia":[501],"gum":[503],"pain":[504,507],"abdominal":[506],"pneumonitis":[509],"febrile":[512],"neutropenia":[513],"(2).":[514],"achieved":[520,566],"CR":[521],"went":[523],"allogeneic":[526],"SCT.":[527],"(2":[530],"FLTwt)":[534],"response":[538,562,627],"(a":[539],"\u226550%":[540],"bone":[543],"marrow":[544],"reduction)":[546],"these":[550],"ultimately":[552],"progressing":[553],"discontinuing":[556],"toxicity.":[559],"Overall":[560],"better":[564,629],"4/29":[568],"(14%),":[570],"had":[573,579],"stable":[574],"disease,":[575],"17":[577],"progressive":[580,616],"disease":[581,617],"less":[584,597],"than":[585,598,639],"days":[587,600],"therapy":[589,602],"(6).":[590],"reasons":[603],"termination":[606],"(1)":[610],"toxicity":[614],"physician":[620],"decision":[621],"incidence":[624],"FLT3mut":[631],"(4/18,":[633],"22%)":[634],"clearly":[637],"higher":[638],"observed":[641],"other":[643],"involving":[645],"agent.":[656],"Pharmacokinetic":[657],"data":[660],"are":[661],"being":[662],"analyzed,":[663],"though":[664],"least":[666],"one":[667],"patient's":[668],"revealed":[670],"treatment-related":[672],"phospho":[676],"FLT3/FLT3":[677],"ratio,":[678],"suggesting":[679],"Conclusion:":[682],"(50":[687],"BID)":[689],"(5":[692],"QOD)":[694],"tolerable":[696],"efficacy":[699],"it":[703],"unclear":[705],"whether":[706],"analog":[712],"results":[713],"superior":[715],"outcomes":[716],"compared":[717],"alone.":[720],"Disclosures:":[721],"Stone:":[722],"Novartis:":[723],"Consultancy,":[724,734],"Research":[725,735],"Funding.":[726,736],"Off":[727],"Label":[728],"Use:":[729],"evorlimus":[730],"AML.":[732],"Griffin:Novartis:":[733],"DeAngelo:Novartis:":[737],"Consultancy.":[738]},"counts_by_year":[{"year":2022,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2017,"cited_by_count":2}],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2019-10-18T00:00:00"}