{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:07:42Z","timestamp":1788444462039,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>This multicenter, open\u2010label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed\/refractory (r\/r) B\u2010cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three\u2010part study are reported. Treatment was a single dose of 100\u00a0mg acalabrutinib (day 1), followed by a washout period and then twice daily 100\u00a0mg acalabrutinib in part 1, or twice daily 100\u00a0mg acalabrutinib in part 2. Patients from parts 1 and 2 with r\/r chronic lymphocytic leukemia (CLL)\/small lymphocytic lymphoma (SLL), and r\/r mantle cell lymphoma (MCL) were assessed as r\/r CLL\/SLL and r\/r MCL cohorts, respectively. Twenty\u2010five patients received treatment (part 1, n\u00a0=\u00a06). Median age was 71.0\u00a0years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r\/r CLL\/SLL and r\/r MCL cohorts, respectively. Treatment\u2010related adverse events (AEs) occurred in 88% of patients (grade\u00a0\u22653, 36%); the most common were headache (28%) and purpura (24%), both grade 1\/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7\u00a0months for part 1, r\/r CLL\/SLL cohort, and r\/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r\/r CLL\/SLL and r\/r MCL cohorts, respectively. The median progression\u2010free survival (PFS) was not reached for the r\/r CLL\/SLL cohort and was 7\u00a0months for the r\/r MCL cohort. Acalabrutinib (100\u00a0mg twice daily) was generally safe and well\u2010tolerated in adult Japanese patients with B\u2010cell malignancies.<\/jats:p>","DOI":"10.1111\/cas.14886","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T06:40:36Z","timestamp":1615963236000},"page":"2405-2415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety and antitumor activity of acalabrutinib for relapsed\/refractory B\u2010cell malignancies: A Japanese phase I study"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[{"name":"National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[{"name":"Tokai University Hospital Isehara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ennishi","sequence":"additional","affiliation":[{"name":"Okayama University Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-2815","authenticated-orcid":false,"given":"Hirohiko","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Osaka University Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Suzumiya","sequence":"additional","affiliation":[{"name":"Shimane University Hospital Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-8955","authenticated-orcid":false,"given":"Kazuhito","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Aichi Cancer Center Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-7197","authenticated-orcid":false,"given":"Satoshi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Tohoku University Hospital Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-4585","authenticated-orcid":false,"given":"Koji","family":"Kato","sequence":"additional","affiliation":[{"name":"Kyushu University Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoya","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Chiba Cancer Center Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Patel","sequence":"additional","affiliation":[{"name":"Acerta Pharma South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6760-152X","authenticated-orcid":false,"given":"Sakura","family":"Iizumi","sequence":"additional","affiliation":[{"name":"AstraZeneca K.K. Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5386-5599","authenticated-orcid":false,"given":"Nobuya","family":"Hayashi","sequence":"additional","affiliation":[{"name":"AstraZeneca K.K Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-2383","authenticated-orcid":false,"given":"Hisashi","family":"Kawasumi","sequence":"additional","affiliation":[{"name":"AstraZeneca K.K. Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-9966","authenticated-orcid":false,"given":"Kosho","family":"Murayama","sequence":"additional","affiliation":[{"name":"AstraZeneca K.K Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Nagai","sequence":"additional","affiliation":[{"name":"National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0313-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00741.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.03.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2741\/vihinen"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2012.664797"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.7906"},{"key":"e_1_2_11_8_1","first-page":"490","article-title":"The Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib (PCI\u201032765), has preferential activity in the activated B cell\u2010like (ABC) subtype of relapsed\/refractory (R\/R) DLBCL: Interim phase 2 results","volume":"1","author":"Vos S","year":"2012","journal-title":"Haematologica"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-526335"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3703"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001160"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-125483"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006844"},{"key":"e_1_2_11_14_1","unstructured":"U.S. Food & Drug Administration. FDA grants accelerated approval to zanubrutinib for mantle cell lymphoma. https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010zanubrutinib\u2010mantle\u2010cell\u2010lymphoma. Accessed January 14 2021."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004594107"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-109973"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509981"},{"key":"e_1_2_11_18_1","unstructured":"U.S. Food & Drug Administration. FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010acalabrutinib\u2010mantle\u2010cell\u2010lymphoma. 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Accessed January 27 2021."},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806398"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2006.n.013"},{"key":"e_1_2_11_29_1","first-page":"1741","article-title":"Pharmacodynamic evaluation of acalabrutinib in relapsed\/refractory and treatment\u2010naive patients with chronic lymphocytic leukemia (CLL) in the phase 1\/2 ACE\u2010CL\u2010001 study","volume":"130","author":"Covey T","year":"2017","journal-title":"Blood"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13076"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14886","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14886","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T19:44:41Z","timestamp":1692560681000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/cas.14886"],"URL":"https:\/\/doi.org\/10.1111\/cas.14886","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]},"assertion":[{"value":"2020-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}