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.
Trial registration:
ClinicalTrials.gov NCT00981240.
Keywords:
AML; MDS; SAR103168; multi-kinase inhibitor.
Publication types
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Clinical Trial, Phase I
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Multicenter Study
MeSH terms
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Acute Disease
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Area Under Curve
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Dizziness / chemically induced
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Dose-Response Relationship, Drug
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Drug Resistance, Neoplasm
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Female
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Humans
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Hypokalemia / chemically induced
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Leukemia, Myeloid / drug therapy*
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Leukemia, Myeloid / pathology
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Male
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Metabolic Clearance Rate
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Middle Aged
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Myelodysplastic Syndromes / drug therapy*
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Myelodysplastic Syndromes / pathology
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Neoplasm Recurrence, Local
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use
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Pyridines / adverse effects
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Pyridines / pharmacokinetics
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Pyridines / therapeutic use*
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Pyrimidines / adverse effects
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Pyrimidines / pharmacokinetics
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Pyrimidines / therapeutic use*
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Risk Factors
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Treatment Outcome
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Young Adult
Substances
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Protein Kinase Inhibitors
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Pyridines
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Pyrimidines
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SAR103168
Associated data
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ClinicalTrials.gov/NCT00981240