Abstract
Subsets of non-acute promyelocytic leukemia (APL) acute myelogenous leukemia (AML) exhibit aberrant retinoid signaling and demonstrate sensitivity to retinoids in vitro. We present the results of a phase 1 dose-escalation study that evaluated the safety, pharmacodynamics, and efficacy of IRX195183, a novel retinoic acid receptor α agonist, in patients with relapsed or refractory myelodysplastic syndrome (MDS) or AML. In this single center, single arm study, eleven patients with relapsed or refractory MDS/AML were enrolled and treated. Oral IRX195183 was administered at two dose levels: 50 mg daily or 75 mg daily for a total of two 28-day cycles. Patients with stable disease or better were allowed to continue on the drug for four additional 28-day cycles. Common adverse events included hypertriglyceridemia, fatigue, dyspnea, and edema. Three patients at the first dose level developed asymptomatic Grade 3 hypertriglyceridemia. The maximally tolerated dose was not reached. Four of the eleven patients had (36%) stable disease or better. One had a morphological complete remission with incomplete hematologic recovery while on the study drug. Two patients had evidence of in vivo leukemic blast maturation, as reflected by increased CD3...Continue Reading
References
Jan 1, 1995·Journal of Cancer Research and Clinical Oncology·Y HashimotoK Shudo
Dec 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
Sep 24, 2004·Leukemia·R F SchlenkUNKNOWN AML Study Group Ulm
Feb 18, 2006·Blood·Donald W MilliganUNKNOWN NCRI Haematological Oncology Clinical Studies Group
Apr 13, 2006·Blood·Bruce D ChesonHagop Kantarjian
Feb 23, 2007·Cancer·Alan K BurnettKeith Wheatley
Feb 27, 2008·Blood·Zhen-Yi Wang, Zhu Chen
Jun 10, 2008·Current Opinion in Hematology·Steven J Collins
Dec 8, 2009·Blood·Alan K BurnettRosemary E Gale
Jun 2, 2010·Biochemical Pharmacology·Jayne E ThatcherNina Isoherranen
Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Gabriel GhiaurRichard J Jones
Apr 29, 2015·Oncotarget·Salvador AlonsoGabriel Ghiaur
Jun 6, 2015·PloS One·Meng SuGabriel Ghiaur
Jul 25, 2015·British Journal of Haematology·David SanfordJorge E Cortes
Mar 10, 2016·The Journal of Experimental Medicine·Héléna BoutzenJean-Emmanuel Sarry
Nov 4, 2016·Annals of Hematology·Richard F SchlenkUNKNOWN German-Austrian Acute Myeloid Leukemia Study Group
Oct 25, 2016·The Journal of Clinical Investigation·Salvador AlonsoGabriel Ghiaur
Mar 10, 2017·The Journal of Pharmacology and Experimental Therapeutics·Jing JingNina Isoherranen
Jul 22, 2017·Cancer Discovery·Michael R McKeownRavindra Majeti
Jul 30, 2017·Experimental Hematology·Salvador AlonsoGabriel Ghiaur
Aug 11, 2018·Leukemia·Akihiro TakeshitaUNKNOWN and the Japanese Adult Leukemia Study Group
Apr 27, 2019·Cell Research·Vera MugoniPier Paolo Pandolfi
Mar 11, 2020·Leukemia·Daniela HernandezGabriel Ghiaur