Developing and Treating a Mouse Model of Acute Myeloid Leukemia Using Tissue Samples From Younger Patients With Acute Myeloid Leukemia

Completed

• Conditions: Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies
• Interventions: Other: laboratory biomarker analysis; Drug: quizartinib; Drug: sorafenib tosylate

• Registration Number: NCT01576185
• Lead Sponsor: Children's Oncology Group

Brief Summary

These laboratory trial studies the development and treatment of a mouse model for acute myeloid leukemia (AML) using samples from younger patients with AML. Studying tissue samples from patients with cancer in the laboratory may help doctors learn more about cancer and how well patients will respond to treatment.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the rate of engraftment of pediatric FMS-Like Tyrosine Kinase-3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) samples in NOD scid gamma (NSG) mice.

II. To determine the efficacy of treatment of FLT3-ITD xenografts with tyrosine kinase inhibitors.

OUTLINE:

Human acute myeloid leukemia cells are injected into NSG mice. Mice are then treated with sorafenib or quizartinib via gavage once daily for 28 days. Peripheral blood and tissue samples are collected biweekly or weekly and analyzed for the presence of human CD45+ and CD33+ cells by quantitative flow cytometry.

Study Timeline

• Study First Submitted: 2012-04-11
• Study First Submitted QC: 2012-04-11
• Study First Posted: 2012-04-12
• Study Start: 2012-05
• Status Verified: 2016-05
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Last Update Submitted: 2016-05-13
• Last Update Posted: 2016-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Cryopreserved human AML samples

  • FLT3-ITD samples with high allelic ratios

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (xenograft models)	sorafenib tosylate	Human acute myeloid leukemia cells are injected into NSG mice. Mice are then treated with sorafenib or quizartinib via gavage once daily for 28 days. Peripheral blood and tissue samples are collected biweekly or weekly and analyzed for the presence of human CD45+ and CD33+ cells by quantitative flow cytometry.
Observational (xenograft models)	laboratory biomarker analysis	Human acute myeloid leukemia cells are injected into NSG mice. Mice are then treated with sorafenib or quizartinib via gavage once daily for 28 days. Peripheral blood and tissue samples are collected biweekly or weekly and analyzed for the presence of human CD45+ and CD33+ cells by quantitative flow cytometry.
Observational (xenograft models)	quizartinib	Human acute myeloid leukemia cells are injected into NSG mice. Mice are then treated with sorafenib or quizartinib via gavage once daily for 28 days. Peripheral blood and tissue samples are collected biweekly or weekly and analyzed for the presence of human CD45+ and CD33+ cells by quantitative flow cytometry.

Primary Outcome Measures

Name	Time	Method
Engraftment ratio of human AML cells to murine cells	Up to 9 months	We will measure total leukemic burden from harvested femurs, tibias, and spleen by quantitative flow cytometry, estimate engraftment, and describe 95% confidence intervals. The total AML cell count of the control and treatment cohorts will be compared using an analysis of variance (ANOVA) test.
Efficacy of sorafenib or quizartinib to inhibit AML proliferation in vivo	Up to 9 months

Trial Locations

Locations (1)

Children's Oncology Group; 🇺🇸 Monrovia, California, United States