This research study is studying lestaurtinib with or with chemotherapy in samples from young patients with leukemia. Studying the effects of lestaurtinib with or without chemotherapy in cell samples from patients with cancer in the laboratory may help doctors learn more about the effects of this treatment on cancer cells. It may also help doctors identify biomarkers related to cancer.
PRIMARY OBJECTIVES: I. Determine the potential of lestaurtinib with or without chemotherapy agents in treating samples from infants with leukemia. II. Determine whether FLT3 protein expression level and/or activation and sensitivity to lestaurtinib differ between subgroups of infants with leukemia. III. Determine whether lestaurtinib activates STAT5, AKT, and RAS-MAPK and other pathways. IV. Determine whether lestaurtinib can synergize with other chemotherapy agents kill infant leukemia cells. OUTLINE: This is a multicenter study. Cryopreserved specimens are studied in vitro with lestaurtinib with or without chemotherapy agents. Samples are analyzed for FLT3 protein expression and/or activation; sensitivity to lestaurtinib with or without chemotherapy agents; and activation of STAT, AKT, and RAS-MAPK and other pathways by western blot. The most effective treatment from this study is then validated in vivo in a NOD/SCID xenograft model.
Study Type
OBSERVATIONAL
Enrollment
18
Samples are analyzed in laboratory studies
Children's Oncology Group
Monrovia, California, United States
Expression level and activation state of FLT3 protein, determined by Western blotting and FACS
Time frame: Up to 4 months
TKI sensitivity, determined by MTT and annexin V assays
Time frame: Up to 4 months
Baseline activation and inhibition of STAT5, AKT, and RAS-MAPK and other pathways, examined with Western blotting and phosphospecific antibodies
Time frame: Baseline
Incidence of cell death in primary infant leukemia samples treated with sequenced combinations of chemotherapy and FLT3 TKI using MTT and annexin V binding assays and median effect analysis
Time frame: Up to 4 months
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