A Multi-Center Phase 2 Study of VEGF Trap as a Single Agent in Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title: A Multi-Center Phase 2 Study of Vascular Endothelial Growth Factor (VEGF) Trap as a Single Agent in Acute Myeloid Leukemia

Status Withdrawn

Clinical Trial Summary

RATIONALE: Aflibercept may stop the growth of cancer cells by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying how well aflibercept works in treating patients with advanced refractory, relapsed, or untreated acute myeloid leukemia.

Clinical Trial Description

OBJECTIVES:

Primary

• To determine the response rate to aflibercept as a single agent in adult patients with advanced refractory, relapsed, or untreated acute myeloid leukemia (AML).

• To determine the 3-month progression-free survival following treatment with at least 4 courses of aflibercept in these patients.

Secondary

• To determine if there is any correlation between pre-treatment expression of VEGFR1 or VEGFR2 by marrow myeloblasts and disease response to aflibercept.

• To determine if bone marrow microvessel density (MVD) pre-treatment correlates with disease response to aflibercept, and if any decrease in MVD following treatment correlates with changes in bone marrow blast percentage (disease response).

• To assess changes in circulating endothelial cells (CEC) and circulating endothelial progenitor cells (EPC) as pharmacodynamic markers of aflibercept activity and possible correlates of disease response to aflibercept.

• To measure blood levels of free VEGF versus VEGF bound by aflibercept post-treatment to determine if the chosen dose of aflibercept is sufficient to bind all detectable soluble VEGF in these patients.

• To characterize the population pharmacokinetics of aflibercept with its associated interpatient variability and to explore for demographic and clinical covariates.

• To derive individual estimates of the duration over which VEGF-saturating aflibercept concentrations were systematically present and to examine their distribution across the population.

• To explore the potential relationship between the systemic-free and bound aflibercept levels and safety and efficacy data.

OUTLINE: This is a multicenter study.

Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow and blood sample collection periodically for pharmacokinetic/pharmacodynamic studies. Samples are analyzed for peak plasma-free aflibercept levels after the first infusion, trough plasma-free and bound aflibercept levels prior to each subsequent infusion and 60 days after the last infusion, and anti-aflibercept antibody via ELISA methods; circulating endothelial cells (CEC's) via ELISA and flow cytometry to determine if there is correlation between changes in circulating endothelial cells and changes in bone marrow blast percentage (i.e., disease response); myeloblast expression of VEGFR-1 and VRGFR-2 via immunohistochemistry (IHC); endothelial progenitor cells colony forming units (EPC-CFU's) to determine via in situ staining if changes in circulating endothelial progenitors following treatment with aflibercept correlates with disease response, and if there is a subpopulation of patients identified by pre-treatment circulating EPC-CFU's that may benefit from aflibercept; and bone marrow microvessel density (MVD) determination via immunohistochemistry.

After completion of study treatment, patients are followed for 60 days. ;

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT00601991
• Study type: Interventional
• Source: Vanderbilt-Ingram Cancer Center
• Status: Withdrawn
• Phase: Phase 2
• Start date: March 2007
• Completion date: October 2009