PMID- 31888052
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 1
DP  - 2019 Dec 26
TI  - 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.
LID - 10.3390/cancers12010074 [doi]
LID - 74
AB  - 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/m(2) was defined as the MTD of OXi4503 when 
      administered in combination with 1 g/m(2) 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.
FAU - Uckun, Fatih M
AU  - Uckun FM
AD  - Immuno-Oncology Program, Mateon Therapeutics, Agoura Hills, CA 91301, USA.
AD  - Ares Pharmaceuticals, St. Paul, MN 55110, USA.
FAU - Cogle, Christopher R
AU  - Cogle CR
AUID- ORCID: 0000-0001-5422-6863
AD  - Division of Hematology and Oncology, Department of Medicine, College of Medicine 
      & University of Florida Health Cancer Center, University of Florida, Gainesville, 
      FL 32610, USA.
FAU - Lin, Tara L
AU  - Lin TL
AUID- ORCID: 0000-0002-0242-6449
AD  - 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.
FAU - Qazi, Sanjive
AU  - Qazi S
AD  - Bioinformatics Program and Department of Biology, Gustavus Adolphus College, St 
      Peter, MN 56082, USA.
FAU - Trieu, Vuong N
AU  - Trieu VN
AD  - Immuno-Oncology Program, Mateon Therapeutics, Agoura Hills, CA 91301, USA.
FAU - Schiller, Gary
AU  - Schiller G
AD  - Bone Marrow/Stem Cell Transplantation, Department of Medicine, David Geffen 
      School of Medicine at UCLA, Los Angeles, CA 90095, USA.
FAU - Watts, Justin M
AU  - Watts JM
AD  - Department of Medicine, Division of Hematology/Oncology Miller School of 
      Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 
      33136, USA.
LA  - eng
PT  - Journal Article
DEP - 20191226
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7016810
OTO - NOTNLM
OT  - AML
OT  - OXA
OT  - clinical study
OT  - combretastatin
OT  - leukemia
COIS- The four institutions received funding from Mateon Therapeutics for conducting 
      the study. F.M.U. and V.N.T. are employees and shareholders of Mateon 
      Therapeutics, the sponsor for clinical development of OXi4503. S.Q. received 
      compensation from Mateon Therapeutics as a consultant. No other disclosures are 
      reported.
EDAT- 2020/01/01 06:00
MHDA- 2020/01/01 06:01
PMCR- 2019/12/26
CRDT- 2020/01/01 06:00
PHST- 2019/12/02 00:00 [received]
PHST- 2019/12/17 00:00 [revised]
PHST- 2019/12/20 00:00 [accepted]
PHST- 2020/01/01 06:00 [entrez]
PHST- 2020/01/01 06:00 [pubmed]
PHST- 2020/01/01 06:01 [medline]
PHST- 2019/12/26 00:00 [pmc-release]
AID - cancers12010074 [pii]
AID - cancers-12-00074 [pii]
AID - 10.3390/cancers12010074 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Dec 26;12(1):74. doi: 10.3390/cancers12010074.