@article{1d2ae5552cc240a5b90bf8055d4f400f,
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",
abstract = "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–NA), which was significantly longer than the median OS time of 113 days (95% CI: 77–172) 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.",
keywords = "AML, Clinical study, Combretastatin, Leukemia, OXA",
author = "Uckun, {Fatih M.} and Cogle, {Christopher R.} and Lin, {Tara L.} and Sanjive Qazi and Trieu, {Vuong N.} and Gary Schiller and Watts, {Justin M.}",
note = "Funding Information: Acknowledgments: The authors thank the patients who participated in this trial and their families, the co-investigators, nurses, and study coordinators at each of the sites. This study was sponsored by Mateon Therapeutics, which provided OXi4503 and worked with investigators to design the study, as well as collect, analyze, and interpret the data. We thank Dana Hirthler from DSG Inc. (Malvern, PA, USA) for maintaining the database; Bruck Habtemariam, Vladamir Kustanovich and Carla Petro (UCLA), Charles Chen (Miami Sylvester Comprehensive Cancer Center), Emily Laskowski (KUMC), and Christina Cline (University of Florida) for their assistance with study coordination and data management; Atul Gupta and Mohit Kapoor from APCER Life Sciences (Princeton, NJ, USA) for contract pharmacovigilance services; and Julie Plummer and coworkers from Precision for Medicine, Oncology and Rare Disease (Flemington, NJ, USA) for CRO services, including clinical monitoring. This work was supported by Mateon Therapeutics. Funding Information: This study was funded by Mateon Therapeutics Inc., (OTCQB:MATN). CRC was supported by a Scholar in Clinical Research award (2400-13) from the Leukemia and Lymphoma Society and the Spanier Foundation. The authors thank the patients who participated in this trial and their families, the co-investigators, nurses, and study coordinators at each of the sites. This study was sponsored by Mateon Therapeutics, which provided OXi4503 and worked with investigators to design the study, as well as collect, analyze, and interpret the data. We thank Dana Hirthler from DSG Inc. (Malvern, PA, USA) for maintaining the database; Bruck Habtemariam, Vladamir Kustanovich and Carla Petro (UCLA), Charles Chen (Miami Sylvester Comprehensive Cancer Center), Emily Laskowski (KUMC), and Christina Cline (University of Florida) for their assistance with study coordination and data management; Atul Gupta and Mohit Kapoor from APCER Life Sciences (Princeton, NJ, USA) for contract pharmacovigilance services; and Julie Plummer and coworkers from Precision for Medicine, Oncology and Rare Disease (Flemington, NJ, USA) for CRO services, including clinical monitoring. This work was supported by Mateon Therapeutics. Funding Information: Funding: This study was funded by Mateon Therapeutics Inc., (OTCQB:MATN). CRC was supported by a Scholar in Clinical Research award (2400-13) from the Leukemia and Lymphoma Society and the Spanier Foundation. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jan,
doi = "10.3390/cancers12010074",
language = "English (US)",
volume = "12",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",
}