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We conducted a phase 1 study with the combination of sorafenib (a FLT3\u2010ITD inhibitor), plerixafor (a SDF\u20101\/CXCR4 inhibitor), and G\u2010CSF (that cleaves SDF\u20101, CD44, and VLA4). Twenty\u2010eight patients with relapsed\/refractory FLT3\u2010ITD\u2010mutated AML were enrolled from December 2010 to December 2013 at three dose levels of sorafenib (400, 600, and 800\u2009mg twice daily) and G\u2010CSF and plerixafor were administered every other day for seven doses starting on day one. Sorafenib 800\u2009mg twice daily was selected for the expansion phase. While no dose\u2010limiting toxicities (DLT) were encountered in the four\u2010week DLT window, hand\u2010foot syndrome and rash were seen beyond the DLT window, which required dose reductions in most patients. The response rate was 36% (complete response (CR) = 4, complete remission with incomplete platelet recovery (CRp) = 4, complete remission with incomplete hematologic recovery (CRi) = 1, and partial response (PR) = 1) for the intention to treat population. Treatment resulted in 58.4 and 47 mean fold mobilization of blasts and CD34\u2009\/38\u2010 stem\/progenitor cells, respectively, to the circulation. Expression of the adhesion molecules CXCR4, CD44, and VLA4 on circulating leukemia cells correlated negatively with the mobilization of CD34+\/38\u2010, CD34+\/38\u2212\/123+ \u201cprogenitor\u201d cells (all <jats:italic>P<\/jats:italic> \u2264\u2009.002). Mass cytometry analysis of sequential samples from two patients demonstrated resistance emerging early on from sub\u2010clones with persistent Akt and\/or ERK signaling. In conclusion, the strategy of combined inhibition of FLT3 kinase and stromal adhesive interactions has promising activity in relapsed\/refractory, FLT3\u2010ITD\u2010mutated AML, which warrants further evaluation in the front\u2010line setting.<\/jats:p>","DOI":"10.1002\/ajh.25943","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T15:52:32Z","timestamp":1595433152000},"page":"1296-1303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Phase 1 study of combinatorial sorafenib, <scp>G\u2010CSF<\/scp>, and plerixafor treatment in relapsed\/refractory, <scp>FLT3\u2010ITD<\/scp>\u2010mutated acute myelogenous leukemia patients"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-6453","authenticated-orcid":false,"given":"Gautam","family":"Borthakur","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD 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