A Multi-Center Phase 2 Study of Vascular Endothelial Growth Factor (VEGF) Trap as a Single Agent in Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Response rate of aflibercept
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Response rate of aflibercept
时间窗: day 14 of cycle 4 (14-day cycle)
As determined by the International Working Group: Complete response: bone marrow blast(BMB) percentage (%) \<=5% of nucleated cells and no detectable extramedullary disease; Partial response: BMB \>5% but decreased by at least 50% pre-treatment (pre-tx) value OR extramedullary disease still present; Stable disease: BMB \>5% and decreased or increased by \<50% of pre-tx value and no new extramedullary disease; Progressive disease: BMB \>=20% and an increase of at least 50% of pre-tx value and/or appearance of at least 50% in circulating blasts
次要结局
- Progression-free survival in patients who achieve either a complete or partial response OR stable disease(at 12 weeks)
- Bone marrow microvessel density determination at baseline, after courses 2 and 4 of treatment(at baseline, at day 29 and at day 57)
- Pharmacokinetics of free versus bound VEGF Trap(Before and after 1st infusion on day 1, before infusion on day 1 of each 14-day cycle, and 60 days after last dose)
研究者
Stephen Strickland
Assistant Professor of Medicine; Hematologist/Oncologist
Vanderbilt-Ingram Cancer Center