@article{137b8465877d4d1da4c74c3f1088494c,
title = "Combination of dociparstat sodium (DSTAT), a CXCL12/CXCR4 inhibitor, with azacitidine for the treatment of hypomethylating agent refractory AML and MDS",
abstract = "Leukemia stem cells utilize cell adhesion molecules like CXCR4/CXCL12 to home to bone marrow stromal niches where they are maintained in a dormant, protected state. Dociparstat sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action, including inhibition of the CXCR4/CXCL12 axis, blocking HMGB1, and binding platelet factor 4 (PF-4). We conducted a pilot study adding DSTAT to azacitidine for patients with AML or MDS unresponsive to or relapsed after prior hypomethylating agent therapy, hypothesizing that DSTAT may improve response rates. Twenty patients were enrolled, with a median of 2 prior lines of therapy and 6 cycles of prior hypomethylating agents. Among fifteen patients evaluable for response, there was 1 complete remission, and 3 marrow complete remissions, for a response rate of 27 % among evaluable patients (20 % overall). Hematologic improvement was observed in 5 additional patients. The median overall survival for all enrolled patients was 205 days (95 % CI 119–302). While cytopenias and infections were common, these were not out of proportion to what would be expected in this population of patients undergoing treatment with azacitidine alone. In summary, this trial demonstrated the feasibility of combining DSTAT with azacitidine, with several responses observed, suggesting this combination warrants further study.",
keywords = "Azacitidine, CX-01, CXCL12, CXCR4, DSTAT, Dociparstat sodium",
author = "Eric Huselton and Rettig, {Michael P.} and Kirsten Campbell and Cashen, {Amanda F.} and DiPersio, {John F.} and Feng Gao and Jacoby, {Meagan A.} and Iskra Pusic and Rizwan Romee and Schroeder, {Mark A.} and Uy, {Geoffrey L.} and Stephen Marcus and Peter Westervelt",
note = "Funding Information: This clinical trial was funded by Cantex Pharmaceuticals . Data collection, analysis, and interpretation was performed independent of the funding source. Funding Information: Geoffrey Uy is a Scholar in Clinical Research of the Leukemia & Lymphoma Society. Supported by a National Cancer Institute (NCI) Outstanding Investigator Award ( R35 CA210084 , to JFD) and NCI Research Specialist Award ( R50 CA211466 , to MPR). Funding Information: This clinical trial was funded by Cantex Pharmaceuticals. Data collection, analysis, and interpretation was performed independent of the funding source.JFD serves on the scientific advisory board and is an equity stakeholder in Magenta Therapeutics. MAJ has received clinical trial funding from Jazz Pharmaceuticals. MAS has received research funding from Genetech Inc,Incyte,Cellect Inc,Equillium Inc,Fortis,Seattle Genetics,Amgen,Celgene,PBD incorporated,Genzyme Sanofi, andJanssenand has served on an advisory board and received honoraria or consulting fees from Amgen, Astellas, Dova pharmaceuticals, Equilium Inc, FlatIron Inc, GSK, Gilead Sciences Inc, Incyte, Janssen, Novo Nordisk, Partners Therapeutics, Pfizer, and Sanofi Genzyme. GLU received consulting fees from Novartis, Abbvie, GSK, Jazz Pharmaceuticals, and Astellas. SM is employed at Cantex Pharmaceuticals. PW has received consulting fees from Pfizer. All other authors declare no relevant conflicts of interest.Geoffrey Uy is a Scholar in Clinical Research of the Leukemia & Lymphoma Society. Supported by a National Cancer Institute (NCI) Outstanding Investigator Award (R35 CA210084, to JFD) and NCI Research Specialist Award (R50 CA211466, to MPR). Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = nov,
doi = "10.1016/j.leukres.2021.106713",
language = "English",
volume = "110",
journal = "Leukemia Research",
issn = "0145-2126",
}