A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Confirmed Complete Response (CR) Rate
研究概览
简要总结
Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving the drug in different ways may kill more cancer cells. This randomized phase II trial is studying two different schedules of vorinostat to see how well they work in treating patients with acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. Determine the toxicity and the proportion of complete remissions associated with two different treatment schedules of vorinostat (SAHA) in patients with acute myeloid leukemia.
SECONDARY OBJECTIVES:
I. Determine the toxic effects of SAHA in this study population. II. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease status (relapsed vs untreated). Patients are randomized to 1 of 2 treatment arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 acute myeloid leukemia (AML), meeting 1 of the following criteria:
- •Relapsed AML in the following categories:
- •Good-risk cytogenetics [inv(16), t (8;21)] in second relapse or in first relapse following a remission of < 12 months
- •Acute promyelocytic leukemia (M3) in second relapse or greater AND must have relapsed following both tretinoin-anthracycline-based therapy and arsenic trioxide-based therapy
- •All other relapsed patients are eligible
- •Untreated AML in the following categories:
- •At least 65 years of age
- •Myelodysplastic syndromes-AML (AML with trilineage dysplasia)
- •AML with del5Q or monosomy 5, monosomy 7, or complex cytogenetics (≥ 3 cytogenetic abnormalities)
- •Refused or ineligible for potentially curative options such as allogeneic stem cell transplantation
- •No clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
- •ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%
- •Life expectancy ≥ 3 months
- •Bilirubin normal unless attributed to hemolysis or Gilbert's disease in the opinion of the investigator
- •AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
- •No uncontrolled intercurrent illness, including any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known HIV positivity
- •More than 4 weeks since prior radiotherapy
- •More than 2 weeks since prior valproic acid
- •More than 3 weeks since other prior treatment for AML, including hematopoietic growth factors
- •Hydroxyurea for WBC > 30,000/mm^3 allowed
- •Recovered from prior therapy
- •No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), epoetin alfa, or darbepoetin alfa
- •No other concurrent investigational agents
- •No other concurrent anticancer agents or therapies for this cancer
排除标准
- 未提供
研究组 & 干预措施
Arm I (once daily vorinostat)
Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Arm II (thrice daily vorinostat)
Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
结局指标
主要结局
Confirmed Complete Response (CR) Rate
时间窗: Up to 2 years
The confirmed complete response rate was estimated by the number of participants with CR divided by the total number of evaluable participants. According to the International Working Group (IWG) Criteria for response in AML, to be considered a CR, the following must be met for at least 4 weeks: ANC \> 1500/mL, platelets \> 100000/mL, no circulating blasts, bone marrow cellularity \>20% (biopsy), trilineage maturation, \< 5% bone marrow blasts, no auer rods and no extramedullary disease.
次要结局
- Time to Progression (TTP)(Duration of study (up to 2 years))
- Overall Survival (OS)(Duration of study (up to 2 years))
- Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events(Duration of study (up to 2 years))