title: Phase I trial of SAR103168, a novel multi-kinase inhibitor, in patients with refractory/relapsed acute leukemia or high-risk myelodysplastic syndrome.
abstract: There is no effective treatment for relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We conducted a phase I dose escalation trial of SAR103168, a novel multi-targeted kinase inhibitor with activity against the Src kinase family, the BCR-Abl kinase and several angiogenic receptor kinases. Twenty-nine patients 18-83 years old were treated with SAR103168. Pharmacokinetics was characterized by plasma peak concentration (Cmax) at the end of the infusion, followed by a biphasic decline in the elimination profile. Adverse events were as expected for the patient population and there were no individual toxicities specific to SAR103168. Due to the unpredictable nature of drug exposure, the sponsor decided to discontinue the study prior to reaching the maximum tolerated dose.
authors.affiliation: Department of Medicine, Weill Medical College of Cornell University , New York, NY , USA.
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Wilena
authors.initials: W
authors.lastname: Session
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Ritchie
authors.forename: Harry
authors.initials: H
authors.lastname: Miao
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: Martha
authors.initials: M
authors.lastname: Arellano
authors.forename: J Gilmour
authors.initials: JG
authors.lastname: Morrison
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C586184:SAR103168
keywords: AML; MDS; SAR103168; multi-kinase inhibitor