{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:10:00Z","timestamp":1781025000410,"version":"3.54.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Gemtuzumab ozogamicin (GO) is indicated for treatment of relapsed\/refractory (R\/R) acute myeloid leukemia (AML). The QT interval, pharmacokinetics (PK), and immunogenicity following the fractionated GO dosing regimen have not been previously assessed. This phase IV study was designed to obtain this information in patients with R\/R AML.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients aged\u2009\u2265\u200918\u00a0years with R\/R AML received the fractionated dosing regimen of GO 3\u00a0mg\/m<jats:sup>2<\/jats:sup> on Days 1, 4, and 7 of each cycle, up to 2 cycles. The primary endpoint was mean change from baseline in QT interval corrected for heart rate (QTc).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Fifty patients received\u2009\u2265\u20091 dose of GO during Cycle 1. The upper limit of the 2-sided 90% confidence interval for least squares mean differences in QTc using Fridericia\u2019s formula (QTcF) was\u2009&lt;\u200910\u00a0ms for all time points during Cycle 1. No patients had a post-baseline QTcF\u2009&gt;\u2009480\u00a0ms or a change from baseline\u2009&gt;\u200960\u00a0ms. Treatment-emergent adverse events (TEAEs) occurred in 98% of patients; 54% were grade 3\u20134. The most common grade 3\u20134 TEAEs were febrile neutropenia (36%) and thrombocytopenia (18%). The PK profiles of both conjugated and unconjugated calicheamicin mirror that of total hP67.6 antibody. The incidence of antidrug antibodies (ADAs) and neutralizing antibodies was 12% and 2%, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Fractionated GO dosing regimen (3\u00a0mg\/m<jats:sup>2<\/jats:sup>\/dose) is not predicted to pose a clinically significant safety risk for QT interval prolongation in patients with R\/R AML. TEAEs are consistent with GO\u2019s known safety profile, and ADA presence appears unassociated with potential safety issues.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registry<\/jats:title>\n                <jats:p>Clinicaltrials.gov ID: NCT03727750 (November 1, 2018).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-023-04516-9","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T09:04:35Z","timestamp":1678352675000},"page":"441-446","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A phase IV study evaluating QT interval, pharmacokinetics, and safety following fractionated dosing of gemtuzumab ozogamicin in patients with relapsed\/refractory CD33-positive acute myeloid leukemia"],"prefix":"10.1007","volume":"91","clinical-trial-number":[{"clinical-trial-number":"nct03727750","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-5593","authenticated-orcid":false,"given":"Pau","family":"Montesinos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsi","family":"Kota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Brandwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bousset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Benner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Vandendries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Frances","family":"McMullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"4516_CR1","doi-asserted-by":"publisher","first-page":"e171","DOI":"10.1634\/theoncologist.2019-0025","volume":"24","author":"S Ali","year":"2019","unstructured":"Ali S, Dunmore HM, Karres D, Hay JL, Salmonsson T, Gisselbrecht C, Sarac SB, Bjerrum OW, Hovgaard D, Barbachano Y (2019) The EMA review of mylotarg (gemtuzumab ozogamicin) for the treatment of acute myeloid leukemia. 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Accessed 27 Sep 2022"}],"container-title":["Cancer Chemotherapy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-023-04516-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00280-023-04516-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-023-04516-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T02:02:37Z","timestamp":1683165757000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00280-023-04516-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["4516"],"URL":"https:\/\/doi.org\/10.1007\/s00280-023-04516-9","relation":{},"ISSN":["0344-5704","1432-0843"],"issn-type":[{"value":"0344-5704","type":"print"},{"value":"1432-0843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]},"assertion":[{"value":"27 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Pau Montesinos has served as a consultant for Agios, Astellas, Celgene, Daiichi Sankyo, Forma Therapeutics, Glycomimetics, and Tolero Pharmaceutical; has been an advisor for AbbVie, Astellas, Celgene, Daiichi Sankyo, Incyte, Janssen, Karyopharm, Novartis, Pfizer, Sanofi, and Teva; has received research funding from AbbVie, Astellas, Celgene, Daiichi Sankyo, Janssen, Karyopharm, Novartis, Pfizer, and Teva; and has participated in speakers bureau for AbbVie, Astellas, Celgene, Daiichi Sankyo, Incyte, Janssen, Novartis, Pfizer, Sanofi, and Teva. Vamsi Kota has served as a consultant for Novartis and Pfizer; and has received research funding from Incyte. Joseph Brandwein has received honoraria from AbbVie, Amgen, Astellas, Bristol Myers Squibb, Jazz, Pfizer, Roche, and Taiho. Pierre Bousset, Rebecca J. Benner, Erik Vandendries, and Ying Chen are employees of Pfizer and own stock in Pfizer. Mary Frances McMullin has been an advisor for AbbVie, Bristol Myers Squibb, Celgene, and Novartis; has received research funding from AOP Health and Bristol Myers Squibb; and has participated in speakers bureau for AOP Health and Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}