Phase I Trial of Vorinostat (SAHA) in Combination With Alvocidib (Flavopiridol) in Patients With Relapsed, Refractory, or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia With Excess Blasts-2
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of flavopiridol when given together with vorinostat in treating patients with relapsed or refractory acute leukemia or chronic myelogenous leukemia or refractory anemia. Flavopiridol and vorinostat may cause leukemia cells to look more like normal cells, and to grow and spread more slowly. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving flavopiridol together with vorinostat may be an effective treatment for leukemia or refractory anemia.
详细描述
PRIMARY OBJECTIVE:
I. Determine recommended phase II doses for the combination of flavopiridol and vorinostat in patients with acute leukemia, chronic myelogenous leukemia in blast crisis, or refractory anemia with excess blasts-2.
SECONDARY OBJECTIVES:
I. Determine the safety, toxicity, tolerability, and maximum tolerated dose of this drug regimen.
II. Determine the pharmacodynamic and clinical anti-leukemic effects of this drug regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosis of one of the following:
- •Relapsed or refractory acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or acute leukemia unclassifiable) following at least one prior systemic treatment
- •Acute leukemia in a patient 60 years or older (no requirement for prior treatment)
- •Acute leukemia that has evolved from a prior myelodysplastic syndrome
- •Chronic myelogenous leukemia (CML) in blast crisis following prior imatinib mesylate therapy
- •Refractory anemia with excess blasts-2 (RAEB-2)
- •No known CNS leukemia
- •ECOG performance status 0-2
- •WBC < 50,000µL
- •Hydroxyurea and/or leukaphereses may be used to lower WBC
- •Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 50 mL/min
- •Total bilirubin =< 2 times ULN
- •AST/ALT =< 2.5 times ULN
- •QTc interval =< 0.470 seconds
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study participation
- •No other condition that would preclude study participation
- •At least 3 weeks since prior treatment (expect leukaphereses)
- •No valproic acid therapy within the past 2 weeks
- •No prior autologous or allogeneic bone marrow or stem cell transplantation
- •No hydroxyurea use within the past 24 hours
- •No concurrent treatment with other anti-cancer agents or investigational agents
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients will receive a 1-hour infusion of flavopiridol on 5 days in week 1 and vorinostat by mouth three times a day in weeks 1 and 2. Treatment may repeat every 3 weeks for as long as benefit is shown.
干预措施: alvocidib (Drug)
Arm I
Patients will receive a 1-hour infusion of flavopiridol on 5 days in week 1 and vorinostat by mouth three times a day in weeks 1 and 2. Treatment may repeat every 3 weeks for as long as benefit is shown.
干预措施: vorinostat (Drug)
结局指标
主要结局
MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0
时间窗: 21 days
次要结局
未报告次要终点