1. Phase I trial of SAR103168, a novel multi-kinase inhibitor, in patients with refractory/relapsed acute leukemia or high-risk myelodysplastic syndrome.
- Author
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Roboz GJ, Khoury HJ, Jabbour E, Session W, Ritchie EK, Miao H, Faderl S, Zheng W, Feldman EJ, Arellano M, Morrison JG, and Ravandi F
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Aged, 80 and over, Area Under Curve, Dizziness chemically induced, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Female, Humans, Hypokalemia chemically induced, Leukemia, Myeloid pathology, Male, Metabolic Clearance Rate, Middle Aged, Myelodysplastic Syndromes pathology, Neoplasm Recurrence, Local, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Pyridines adverse effects, Pyridines pharmacokinetics, Pyrimidines adverse effects, Pyrimidines pharmacokinetics, Risk Factors, Treatment Outcome, Young Adult, Leukemia, Myeloid drug therapy, Myelodysplastic Syndromes drug therapy, Pyridines therapeutic use, Pyrimidines therapeutic use
- 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.
- Published
- 2015
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