{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:18:07Z","timestamp":1772770687805,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Combretastatin A1 (OXi4503) is a dual-function drug with vascular disrupting and cytotoxic properties that has exhibited single-agent anti-leukemia activity in murine xenograft models of acute myeloid leukemia (AML) and in a prior Phase 1A clinical study for relapsed\/refractory (R\/R) AML. The purpose of the present multicenter Phase 1B study was to define the maximum tolerated dose (MTD) and safety profile of OXi4503 and cytarabine (ARA-C) administered in combination (OXA). At four centers, 29 patients with R\/R AML or myelodysplastic syndrome (MDS) were treated with OXA. The most common grade 3\/4 treatment-emergent adverse events (AEs) were febrile neutropenia (28%), hypertension (17%), thrombocytopenia (17%), and anemia (14%). There were no treatment-emergent grade 5 AEs. Drug-related serious adverse events (SAEs) developed in 4\/29 patients (14%) and included febrile neutropenia (N = 2), pneumonia\/acute respiratory failure (N = 1), and hypotension (N = 1). 9.76 mg\/m2 was defined as the MTD of OXi4503 when administered in combination with 1 g\/m2 ARA-C. In 26 evaluable AML patients, there were 2 complete remissions (CR), 2 complete remissions with incomplete count recovery (CRi) and one partial response (PR), for an overall response rate (ORR) of 19%. The median overall survival (OS) time for the four patients who achieved a CR\/CRi was 528 days (95% CI: 434\u2013NA), which was significantly longer than the median OS time of 113 days (95% CI: 77\u2013172) for the remaining 22 patients who did not achieve a CR\/CRi (Log Rank Chi Square = 11.8, p-value = 0.0006). The safety and early evidence of efficacy of the OXA regimen in R\/R AML patients warrant further investigation in a Phase 2 clinical study.<\/jats:p>","DOI":"10.3390\/cancers12010074","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T05:37:08Z","timestamp":1577425028000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A Phase 1B Clinical Study of Combretastatin A1 Diphosphate (OXi4503) and Cytarabine (ARA-C) in Combination (OXA) for Patients with Relapsed or Refractory Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-183X","authenticated-orcid":false,"given":"Fatih M.","family":"Uckun","sequence":"first","affiliation":[{"name":"Immuno-Oncology Program, Mateon Therapeutics, Agoura Hills, CA 91301, USA"},{"name":"Ares Pharmaceuticals, St. Paul, MN 55110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-6863","authenticated-orcid":false,"given":"Christopher R.","family":"Cogle","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, College of Medicine &amp; University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0242-6449","authenticated-orcid":false,"given":"Tara L.","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies and Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, University of Kansas Cancer Center and Medical Pavillon, Westwood, KS 66205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjive","family":"Qazi","sequence":"additional","affiliation":[{"name":"Bioinformatics Program and Department of Biology, Gustavus Adolphus College, St Peter, MN 56082, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vuong N.","family":"Trieu","sequence":"additional","affiliation":[{"name":"Immuno-Oncology Program, Mateon Therapeutics, Agoura Hills, CA 91301, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Schiller","sequence":"additional","affiliation":[{"name":"Bone Marrow\/Stem Cell Transplantation, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin M.","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology Miller School of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"ref_1","unstructured":"PDQ Adult Treatment Editorial Board (2002). 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