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A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1\/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Sixty-six patients with a median age of 65 (range: 19\u201380) years were enrolled. Cohorts of six and twelve patients were treated in phase 1 with one dose of GO or three doses of GO (GO3) at 3 mg\/m2 per dose. Since a maximum-tolerated dose was not reached, the recommended phase 2 dose (RP2D) was declared to be GO3. At RP2D, 52\/60 (87%) patients achieved a complete remission (CR)\/CR with incomplete hematologic recovery (CRi), 45\/52 (87%) without flow cytometric measurable residual disease (MRD). Eight-week mortality was 0%. Six- and twelve-month event-free survival (EFS) were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M\/GO3 was associated with better survival in patients with favorable-risk disease (EFS: p = 0.007; OS: p = 0.030). These data indicate that CLAG-M\/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML\/high-grade myeloid neoplasm.<\/jats:p>","DOI":"10.3390\/cancers14122934","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T23:50:14Z","timestamp":1655250614000},"page":"2934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phase 1\/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms"],"prefix":"10.3390","volume":"14","author":[{"given":"Colin","family":"Godwin","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, 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Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siob\u00e1n","family":"Keel","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janis","family":"Abkowitz","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Cooper","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Cassaday","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elihu","family":"Estey","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, 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