{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:19:00Z","timestamp":1772986740602,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18lk0201046h0003"],"award-info":[{"award-number":["18lk0201046h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Clinical development of crizotinib in children with ALK\u2010positive anaplastic large cell lymphoma (ALCL) was advanced in the US but not in Japan. The objectives of phase 1 part of a clinical study in Japan were to assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of crizotinib in children with relapsed\/refractory (R\/R) ALK\u2010positive ALCL or neuroblastoma (NB). Two dose levels (165 and 280\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    twice daily (BID)) were planned to be evaluated. The aim of phase 2 part of the study was to assess the antitumor activity of crizotinib at the RP2D in children with R\/R ALK\u2010positive ALCL. Seven patients were eligible for phase 1 part, 5 with ALCL and 2 with NB. All 7 patients received crizotinib at a starting dose of 165\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    BID, with 1 dose\u2010limiting toxicity observed (grade 3 gamma\u2010glutamyltransferase increased). The most common grade 3 or 4 adverse event was neutropenia (71%). The steady\u2010state\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>tau<\/jats:sub>\n                    of crizotinib at 165\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    BID were higher than expected. Considering the risk of a greater incidence of severe neutropenia, we decided that the 165\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    BID be the RP2D without evaluation at 280\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    BID. A total of 11 patients with ALK\u2010positive ALCL were enrolled in the phase 2 part. The objective response rate was 72.7% (90% CI, 43.6%\u201392.1%). One patient permanently discontinued crizotinib due to disease progression. Crizotinib at 165\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    BID was well tolerated and showed favorable antitumor activity in children with R\/R ALK\u2010positive ALCL.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    UMIN\u2010CTR: UMIN000028075\n                  <\/jats:p>","DOI":"10.1111\/cas.70308","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:58:53Z","timestamp":1766991533000},"page":"777-786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase 1\/2 Study of Crizotinib in Children With Relapsed\/Refractory\n                    <scp>ALK<\/scp>\n                    \u2010Positive Anaplastic Large Cell Lymphoma or Neuroblastoma in Japan"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-3196","authenticated-orcid":false,"given":"Tetsuya","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Pediatrics St. Marianna University School of Medicine  Kawasaki Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Kada","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagoya Medical Center  Nagoya Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Osumi","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhki","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Hospital Organization Kyushu Cancer Center  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4087-3426","authenticated-orcid":false,"given":"Reiji","family":"Fukano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamaguchi University Graduate School of Medicine  Yamaguchi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-5800","authenticated-orcid":false,"given":"Kengo","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Pathology Cancer Institute, Japanese Foundation for Cancer Research  Tokyo Japan"},{"name":"Pathology Project for Molecular Targets, Cancer Institute Japanese Foundation for Cancer Research  Tokyo Japan"},{"name":"Department of 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