Temozolomide Plus Vorinostat in Patients With Relapse/Refractory Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Complete Remission (CR)
研究概览
简要总结
The purpose of the study is to first determine if temozolomide plus vorinostat in combination can control relapsed or refractory acute myeloid leukemia (AML) and determine if this combination can be safely taken. The study will look at the side effects of the Temozolomide plus Vorinostat in combination and whether the treatment schedule is tolerated.
详细描述
The primary endpoint of the study is to determine the clinical efficacy as determined by the rate of morphological complete remission, of 2 different treatment regimens of temozolomide and vorinostat administered to 2 distinct groups of participants patients with AML and poor prognostic features. Participants will be allocated to treatment on the basis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
研究组 & 干预措施
Participant Group 1 (methylated MGMT promoter)
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
干预措施: Temozolomide (Drug)
Participant Group 1 (methylated MGMT promoter)
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
干预措施: Vorinostat (Drug)
Participant Group 2 (non-methylated MGMT promoter)
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
干预措施: Temozolomide (Drug)
Participant Group 2 (non-methylated MGMT promoter)
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
干预措施: Vorinostat (Drug)
结局指标
主要结局
Complete Remission (CR)
时间窗: up to 10 weeks
This study evaluates the clinical efficacy of temozolomide + vorinostat as administered to Groups 1 and 2, assessed as the rate of complete remission \[CR, aka morphologic complete remission (mCR)\], defined as the morphologic leukemia-free state (MLFS), WITH absolute neutrophil count (ANC) ≥ 1,000/µL AND platelets (PLT) ≥ 100,000/µL. The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated CR. CR is defined as all of the following. MLFS = \< 5% blasts in bone marrow aspirate containing marrow spicules \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease ANC = ≥ 1,000/µL PLT = ≥ 100,000/µL
次要结局
- Morphologic Leukemia-free State (MLFS)(up to 10 weeks)
- Complete Remission With Incomplete Blood Count Recovery (CRp)(up to 10 weeks)
- Partial Remission (PR)(up to 10 weeks)
- Cytogenetic Response (CyR)(up to 10 weeks)
- Treatment Failure (TF)(up to 10 weeks)
- Overall Survival (OS) at 2 Years(2 years)
- Disease-free Survival (DFS) at 2 Years(2 years)
- Relapse-Free Survival (RFS) at 2 Years(2 years)
研究者
Steven E. Coutre
Professor of Medicine (Hematology)
Stanford University