{"id":"https://openalex.org/W163673794","doi":"https://doi.org/10.1182/blood.v122.21.1443.1443","title":"MLN4924, a Novel Investigational Inhibitor Of NEDD8-Activating Enzyme (NAE), In Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS): Results From Multiple Dosing Schedules In a Phase 1 Study","display_name":"MLN4924, a Novel Investigational Inhibitor Of NEDD8-Activating Enzyme (NAE), In Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS): Results From Multiple Dosing Schedules In a Phase 1 Study","publication_year":2013,"publication_date":"2013-11-15","ids":{"openalex":"https://openalex.org/W163673794","doi":"https://doi.org/10.1182/blood.v122.21.1443.1443","mag":"163673794"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v122.21.1443.1443","doi":"https://doi.org/10.1182/blood.v122.21.1443.1443","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.1443.1443","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/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":false,"raw_author_name":"Daniel J. DeAngelo","raw_affiliation_strings":["Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA,","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050556099","display_name":"Harry Paul Erba","orcid":"https://orcid.org/0000-0003-1093-2189","observed_orcids":["https://orcid.org/0000-0003-1093-2189"]},"institutions":[{"id":"https://openalex.org/I32389192","display_name":"University of Alabama at Birmingham","ror":"https://ror.org/008s83205","country_code":"US","type":"education","lineage":["https://openalex.org/I32389192"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Harry P Erba","raw_affiliation_strings":["The Division of Hematology & Oncology, University of Alabama, Birmingham, AL, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Division of Hematology & Oncology, University of Alabama, Birmingham, AL, USA,","institution_ids":["https://openalex.org/I32389192"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111656515","display_name":"Michael B. Maris","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210134093","display_name":"Colorado Blood Cancer Institute","ror":"https://ror.org/040pncp85","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210134093"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Michael B Maris","raw_affiliation_strings":["Colorado Blood Cancer Institute, Denver, CO, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Colorado Blood Cancer Institute, Denver, CO, USA,","institution_ids":["https://openalex.org/I4210134093"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032988049","display_name":"Ronan T. Swords","orcid":"https://orcid.org/0000-0003-3319-1870","observed_orcids":["https://orcid.org/0000-0003-3319-1870"]},"institutions":[{"id":"https://openalex.org/I145608581","display_name":"University of Miami","ror":"https://ror.org/02dgjyy92","country_code":"US","type":"education","lineage":["https://openalex.org/I145608581"]},{"id":"https://openalex.org/I4210157065","display_name":"Sylvester Comprehensive Cancer Center","ror":"https://ror.org/0552r4b12","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I145608581","https://openalex.org/I4210101935","https://openalex.org/I4210157065"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Ronan T. Swords","raw_affiliation_strings":["Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA,","institution_ids":["https://openalex.org/I145608581","https://openalex.org/I4210157065"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005991606","display_name":"Faiz Anwer","orcid":"https://orcid.org/0000-0001-6914-7439","observed_orcids":["https://orcid.org/0000-0001-6914-7439"]},"institutions":[{"id":"https://openalex.org/I138006243","display_name":"University of Arizona","ror":"https://ror.org/03m2x1q45","country_code":"US","type":"education","lineage":["https://openalex.org/I138006243"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Faiz Anwer","raw_affiliation_strings":["Department of Medicine, Division of Hematology Oncology, University of Arizona, Tucson, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Division of Hematology Oncology, University of Arizona, Tucson, AZ, USA,","institution_ids":["https://openalex.org/I138006243"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025780450","display_name":"Jessica Kaplan Altman","orcid":"https://orcid.org/0000-0003-1987-1896","observed_orcids":["https://orcid.org/0000-0003-1987-1896"]},"institutions":[{"id":"https://openalex.org/I4390039227","display_name":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University","ror":"https://ror.org/02p4far57","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210147348","https://openalex.org/I4390039227"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jessica K Altman","raw_affiliation_strings":["Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA,","institution_ids":["https://openalex.org/I4390039227"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108670559","display_name":"Zhaowei Hua","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405270001","display_name":"Takeda Oncology (United States)","ror":"https://ror.org/05vm7p871","country_code":"US","type":"company","lineage":["https://openalex.org/I4405270001"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Zhaowei Hua","raw_affiliation_strings":["Millennium: The Takeda Oncology Company, Cambridge, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Millennium: The Takeda Oncology Company, Cambridge, MA, USA,","institution_ids":["https://openalex.org/I4405270001"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009761094","display_name":"Stephen J. Blakemore","orcid":"https://orcid.org/0009-0009-8524-3717","observed_orcids":["https://orcid.org/0009-0009-8524-3717"]},"institutions":[{"id":"https://openalex.org/I4405270001","display_name":"Takeda Oncology (United States)","ror":"https://ror.org/05vm7p871","country_code":"US","type":"company","lineage":["https://openalex.org/I4405270001"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Stephen J Blakemore","raw_affiliation_strings":["Millennium: The Takeda Oncology Company, Cambridge, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Millennium: The Takeda Oncology Company, Cambridge, MA, USA,","institution_ids":["https://openalex.org/I4405270001"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041293213","display_name":"H\u00e9l\u00e8ne M. Faessel","orcid":"https://orcid.org/0000-0002-3007-3345","observed_orcids":["https://orcid.org/0000-0002-3007-3345"]},"institutions":[{"id":"https://openalex.org/I4405270001","display_name":"Takeda Oncology (United States)","ror":"https://ror.org/05vm7p871","country_code":"US","type":"company","lineage":["https://openalex.org/I4405270001"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"H\u00e9l\u00e8ne Faessel","raw_affiliation_strings":["Millennium: The Takeda Oncology Company, Cambridge, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Millennium: The Takeda Oncology Company, Cambridge, MA, USA,","institution_ids":["https://openalex.org/I4405270001"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109548084","display_name":"Bruce Jeffrey Dezube","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405270001","display_name":"Takeda Oncology (United States)","ror":"https://ror.org/05vm7p871","country_code":"US","type":"company","lineage":["https://openalex.org/I4405270001"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bruce J Dezube","raw_affiliation_strings":["Millennium: The Takeda Oncology Company, Cambridge, MA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Millennium: The Takeda Oncology Company, Cambridge, MA, USA,","institution_ids":["https://openalex.org/I4405270001"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5000838010","display_name":"Bruno C. Medeiros","orcid":"https://orcid.org/0000-0001-6972-8137","observed_orcids":["https://orcid.org/0000-0001-6972-8137"]},"institutions":[{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Bruno C Medeiros","raw_affiliation_strings":["Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":10,"corresponding_author_ids":["https://openalex.org/A5000838010","https://openalex.org/A5009761094","https://openalex.org/A5032988049","https://openalex.org/A5041293213","https://openalex.org/A5050556099","https://openalex.org/A5108670559","https://openalex.org/A5111656515"],"corresponding_institution_ids":["https://openalex.org/I145608581","https://openalex.org/I32389192","https://openalex.org/I4210134093","https://openalex.org/I4210137306","https://openalex.org/I4210157065","https://openalex.org/I4405270001","https://openalex.org/I97018004"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":1.1834,"has_fulltext":false,"cited_by_count":5,"citation_normalized_percentile":{"value":0.79785994,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"122","issue":"21","first_page":"1443","last_page":"1443"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9761000275611877,"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":0.9761000275611877,"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.01119999960064888,"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.0026000000070780516,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/nedd8-activating-enzyme-inhibitor","display_name":"NEDD8-activating enzyme inhibitor","score":0.9739999771118164},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.906000018119812},{"id":"https://openalex.org/keywords/myelodysplastic-syndrome","display_name":"myelodysplastic syndrome","score":1.0},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.7820000052452087},{"id":"https://openalex.org/keywords/safety-and-tolerability","display_name":"safety and tolerability","score":0.7979999780654907},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.7749999761581421},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"pharmacodynamics","score":0.7419999837875366},{"id":"https://openalex.org/keywords/cullin-ring-e3-ligase","display_name":"Cullin-RING E3 ligases","score":0.9470000267028809},{"id":"https://openalex.org/keywords/complete-response","display_name":"complete response","score":0.3370000123977661}],"concepts":[{"id":"https://openalex.org/C2778850193","wikidata":"https://www.wikidata.org/wiki/Q3775974","display_name":"Febrile neutropenia","level":4,"score":0.6746628284454346},{"id":"https://openalex.org/C2777063308","wikidata":"https://www.wikidata.org/wiki/Q1435822","display_name":"Neutropenia","level":3,"score":0.6533593535423279},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6211329698562622},{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.6136725544929504},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.5431392192840576},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.5344998240470886},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.49223461747169495},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4921721816062927},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4633987247943878},{"id":"https://openalex.org/C31760486","wikidata":"https://www.wikidata.org/wiki/Q7180990","display_name":"Phases of clinical research","level":3,"score":0.4152514934539795},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.41524824500083923},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.35809630155563354},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.27700138092041016}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v122.21.1443.1443","doi":"https://doi.org/10.1182/blood.v122.21.1443.1443","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.1443.1443","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":[{"id":"https://metadata.un.org/sdg/3","score":1.0,"display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/clinical-trial","display_name":"Clinical Trial"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2554823661","https://openalex.org/W2978593427","https://openalex.org/W2552096861","https://openalex.org/W2590196732","https://openalex.org/W2589138686","https://openalex.org/W2062980622","https://openalex.org/W2225775068","https://openalex.org/W2520260850","https://openalex.org/W2537793793","https://openalex.org/W2587482226"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"NEDD8-activating":[2],"enzyme":[3],"(NAE)":[4],"regulates":[5],"the":[6,16,365,430,559,598,648],"NEDD8":[7],"conjugation":[8],"pathway,":[9],"and":[10,36,64,86,138,176,194,202,221,242,263,285,329,348,358,398,413,442,473,484,490,502,558,575,592,617,654],"is":[11,609,637],"required":[12],"for":[13,42,109,154,218,369,505,603,647],"activity":[14,55,583,595],"of":[15,25,44,66,78,88,151,169,188,429,469,475,500,514,538,619,625,650],"cullin-RING":[17],"E3":[18],"ligases":[19],"(CRLs).":[20],"CRLs":[21],"control":[22],"proteasomal":[23],"degradation":[24],"several":[26],"substrates":[27],"involved":[28],"in":[29,56,106,364,481,581,584,607,629],"cell-cycle":[30],"regulation,":[31],"signal":[32],"transduction,":[33],"DNA":[34],"replication":[35],"stress":[37],"response":[38],"including":[39],"proteins":[40],"important":[41],"survival":[43],"AML":[45,58,135,241,284,524,548,631,653],"cells.":[46],"MLN4924,":[47,277],"a":[48,89,145,185,423,551,564,620],"first-in-class":[49],"NAE":[50,576],"inhibitor,":[51],"has":[52],"shown":[53,363],"antitumor":[54],"preclinical":[57],"models.":[59],"This":[60],"study":[61,624],"evaluated":[62],"safety":[63,591],"tolerability":[65],"MLN4924":[67,143,170,189,257,433,579,606,626,646],"given":[68,81,612],"on":[69,82,128,149,171,190,294,387,410,416,508,590,613],"multiple":[70],"dosing":[71],"schedules.":[72,131,510],"A":[73,623],"maximum":[74],"tolerated":[75,574],"dose":[76,187,602],"(MTD)":[77],"59":[79],"mg/m2":[80,265,276,409,492,611],"days":[83,172,191,614],"1,":[84,173,192,615],"3":[85,193,243,616],"5":[87,195,618],"21-day":[90,621],"cycle":[91,216],"(schedule":[92,440,445],"A)":[93],"was":[94,236,280,372,455,460],"previously":[95],"reported":[96],"(Erba":[97],"et":[98],"al,":[99],"EHA":[100],"2011);":[101],"complete":[102],"responses":[103,203,528],"were":[104,204,213,230,390,436,467,486],"observed":[105,593],"4/27":[107],"patients":[108,165,183,229,271,293,311,340,381,405,415,507,517,525,541,632,651],"this":[110],"schedule":[111,226,295,337,411,417,464,512,536],"(most":[112],"common":[113,118,356],"AE:":[114,121],"diarrhea":[115],"[44%],":[116],"most":[117],"Gr":[119,333,359],"\u22653":[120,360],"febrile":[122],"neutropenia":[123],"[33%]).":[124],"Here":[125],"we":[126],"report":[127],"two":[129,152],"additional":[130],"Methods":[132],"Adults":[133],"with":[134,250,289,578,627,652],"or":[136,159,656],"MDS":[137,245,287,560],"good":[139],"performance":[140],"status":[141],"received":[142,166,184,256,274,382],"as":[144,374],"60-min":[146],"IV":[147],"infusion":[148],"one":[150],"schedules":[153,378,568],"up":[155],"to":[156,207,392,570],"1":[157,217,301,544,546],"year":[158],"until":[160],"disease":[161,249,394,557],"progression.":[162],"Schedule":[163,181,268,370,449],"B":[164,296,371,412,450],"escalating":[167],"doses":[168],"4,":[174],"8":[175],"11":[177],"every":[178,196],"21":[179,197],"days.":[180,198],"E":[182,465],"fixed":[186],"Adverse":[199],"events":[200],"(AEs)":[201],"graded":[205],"according":[206],"published":[208],"guidelines.":[209],"Serial":[210],"blood":[211],"samples":[212],"obtained":[214],"during":[215],"pharmacokinetic":[219],"(PK)":[220],"pharmacodynamic":[222],"analyses.":[223],"Results":[224],"On":[225,267,336,377,511,535],"B:":[227],"26":[228],"enrolled":[231],"(77%":[232],"male),":[233],"median":[234,278],"age":[235,279],"70.5":[237,281],"yrs,":[238,282],"23":[239],"had":[240,244,247,297,341,526,532,550,563],"(2":[246],"advanced":[248,290],"marrow":[251],"blasts":[252],"exceeding":[253],"10%).":[254],"Patients":[255],"at":[258,303,312,407],"83":[259,375,408,491],"(n=19),":[260],"110":[261,304],"(n=4),":[262],"147":[264,313],"(n=3).":[266],"E:":[269],"16":[270,414],"(69%":[272],"male)":[273],"50":[275,489,610],"14":[283],"2":[286,310,339,520,522,601],"(1":[288],"disease).":[291],"Three":[292],"dose-limiting":[298],"toxicities":[299],"(DLTs):":[300],"patient":[302,549,561],"mg/m2;":[305,314],"orthostatic":[306],"hypotension":[307],"(Gr":[308,317,345,352],"3);":[309],"cardiac":[315],"failure":[316,328],"4;":[318,334],"n=1),":[319],"fatal":[320],"lactic":[321],"acidosis,":[322],"hypotension,":[323],"gastrointestinal":[324],"necrosis,":[325],"acute":[326],"renal":[327],"myocardial":[330],"ischemia":[331],"(each":[332],"n=1).":[335,354],"E,":[338,418,537],"DLTs:":[342],"morbilliform":[343],"rash":[344],"3;":[346],"n=1);":[347],"increased":[349],"aspartate/alanine":[350],"aminotransferases":[351],"2/3;":[353],"Most":[355],"all-grade":[357],"AEs":[361,396],"are":[362],"table.":[366],"The":[367,660,666,672,678,684],"MTD":[368],"determined":[373],"mg/m2.":[376],"B/E,":[379],"3/2":[380],"\u22654":[383],"cycles,":[384],"0/4":[385],"remain":[386],"treatment;":[388],"discontinuations":[389],"due":[391],"progressive":[393],"(11/10),":[395],"(8/0),":[397],"other":[399],"reasons":[400],"(7/2)":[401],"respectively.":[402],"In":[403],"17":[404],"treated":[406],"individual":[419],"PK":[420],"profiles":[421],"showed":[422],"biphasic":[424],"disposition":[425],"phase":[426,600],"following":[427],"completion":[428],"first":[431],"infusion.":[432],"plasma":[434],"concentrations":[435],"detectable":[437],"24\u201348":[438],"hours":[439,444],"B)":[441],"24":[443],"E)":[446],"post":[447],"dosing.":[448,495],"geometric":[451],"mean":[452,482],"(%CV)":[453],"Cmax":[454,468,483],"1255":[456],"ng/mL":[457,471],"(25.1%),":[458],"AUC24hr":[459,474,485],"3936":[461],"ng\u2022h/mL":[462,477],"(22.6%);":[463],"values":[466],"669":[470],"(24.4%)":[472],"2614":[476],"(21.4%).":[478],"Observed":[479],"increases":[480],"dose-proportional":[487],"between":[488],"after":[493],"single":[494,604],"Pharmacodynamic":[496],"data":[497],"demonstrated":[498],"evidence":[499],"target":[501],"pathway":[503],"inhibition":[504,577],"all":[506],"both":[509],"B,":[513],"20":[515],"response-evaluable":[516,540],"(18":[518],"AML,":[519,543],"MDS),":[521,545],"(11%)":[523],"partial":[527],"(PR),":[529],"13":[530],"(72%)":[531],"stable":[533,556],"disease.":[534],"12":[539],"(11":[542],"(8%)":[547,562],"PR,":[552],"7":[553],"(59%)":[554],"maintained":[555],"response.":[565],"Conclusions":[566],"Both":[567],"appeared":[569],"be":[571],"generally":[572],"well":[573],"resulted":[580],"clinical":[582,594],"highly":[585],"refractory/multiply":[586],"relapsed":[587],"patients.":[588],"Based":[589],"across":[596],"schedules,":[597],"recommended":[599],"agent":[605,645],"AML/MDS":[608],"cycle.":[622],"azacitidine":[628],"treatment-na\u00efve":[630],"older":[633],"than":[634],"60":[635],"years":[636],"ongoing":[638],"(NCT01814826).":[639],"Disclosures:":[640],"Off":[641],"Label":[642],"Use:":[643],"Investigational":[644],"treatment":[649],"high-grade":[655],"low-grade":[657],"MDS.":[658],"Hua:Millennium:":[659],"Takeda":[661,667,673,679,685],"Oncology":[662,668,674,680,686],"Company:":[663,669,675,681,687],"Employment.":[664,670,676,682],"Blakemore:Millennium:":[665],"Faessel:Millennium:":[671],"Dezube:Millennium:":[677],"Medeiros:Millennium:":[683],"Research":[688],"Funding.":[689]},"counts_by_year":[{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":1}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2016-06-24T00:00:00"}