{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:21:22Z","timestamp":1789014082267,"version":"build-2803163510"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"German Research Organization","award":["DFG- SCHL 2118\/2-1"],"award-info":[{"award-number":["DFG- SCHL 2118\/2-1"]}]},{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods\/Design<\/jats:title>\n                <jats:p>This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60\u2009years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 versus GO administered once on day 1 (GO-147 versus GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 +\u20093 schedule with cytarabine 200\u2009mg\/m<jats:sup>2<\/jats:sup> continuously days 1 to 7, daunorubicin 60\u2009mg\/m<jats:sup>2<\/jats:sup> days 1, 2, and 3 and high-dose cytarabine (1\u2009g\/m<jats:sup>2<\/jats:sup>, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Ethics and dissemination<\/jats:title>\n                <jats:p>Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial status<\/jats:title>\n                <jats:p>Protocol version: 1st version 20.10.2020, no amendments yet. Study initiation on February 16, 2021. First patient was recruited on April 1st.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04093505\">NCT04093505<\/jats:ext-link>; EudraCT 2019-003913-32. Registered on October 30, 2018.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-021-05703-w","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T14:09:27Z","timestamp":1636121367000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed 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