Lestaurtinib With or Without Chemotherapy Agents in Samples From Young Patients With Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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SCOR in Targeted Therapies for Infant Leukemia Project 3: Targeting FLT3 in Infant Leukemia

Conditions
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Childhood Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies

Intervention / Treatment
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* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cryopreserved samples from infants with leukemia available

Ages Eligible for Study
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Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational<br>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. | Other: laboratory biomarker analysis<br>* Samples are analyzed in laboratory studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression level and activation state of FLT3 protein, determined by Western blotting and FACS |  | Up to 4 months | 
| TKI sensitivity, determined by MTT and annexin V assays |  | Up to 4 months | 
| Baseline activation and inhibition of STAT5, AKT, and RAS-MAPK and other pathways, examined with Western blotting and phosphospecific antibodies |  | 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 |  | Up to 4 months |