Phase II Study of the Histone Deacetylase Inhibitor PXD101 for the Treatment of Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart
研究概览
简要总结
This phase II trial is studying how well belinostat works in treating patients with myelodysplastic syndromes. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
详细描述
OBJECTIVES:
I. Establish the efficacy and safety of PXD101 (belinostat) in patients with myelodysplastic syndromes that progressed after or is ineligible for azacitidine treatment.
II. Assess the biological activity of PXD101 in these patients via assays of histone acetylation, gene expression profiling, and DNA methylation.
OUTLINE: This is a multicenter study.
Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response, partial response, or hematologic improvement after 4 courses receive 4 additional courses of therapy. After completion of study treatment, patients are followed every 3-6 months for up to 3 years.
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
- •Histologically confirmed myelodysplastic syndromes (MDS)
- •De novo or secondary MDS
- •Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria:
- •Symptomatic anemia with either hemoglobin < 10.0 g/dL or required RBC transfusions within the past 3 months
- •Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ or significant hemorrhage requiring platelet transfusions
- •Neutropenia with ≥ 2 absolute neutrophil counts < 1,000/mm³
- •No acute myeloid leukemia (≥ 20% bone marrow blasts)
- •ECOG performance status 0-2
- •Life expectancy > 12 weeks
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST ≤ 2 times ULN
- •Creatinine ≤ 2.0 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
- •No HIV positivity
- •QTc interval ≤ 500 msec
- •No long QT syndrome
- •No significant cardiovascular disease, including any of the following:
- •Unstable angina pectoris
- •Uncontrolled hypertension
- •Congestive heart failure related to primary cardiac disease
- •Condition requiring anti-arrhythmic therapy
- •Ischemic or severe valvular heart disease
- •Myocardial infarction within the past 6 months
- •No other uncontrolled serious medical condition (e.g., cardiac arrhythmias or diabetes)
- •Recovered from prior therapy
- •No more than 2 prior therapies for MDS
- •Prior hematopoietic growth factors, androgens, and other supportive care agents allowed and are not considered in the prior therapy total
- •No prior allogeneic stem cell transplantation
- •More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- •No prior histone deacetylase (HDAC) inhibitors for treatment of MDS
- •More than 2 weeks since prior valproic acid or other HDAC inhibitors
- •No other concurrent investigational agents
- •No concurrent medication that may cause torsades depointes, including any of the following:
- •Disopyramide
- •Dofetilide
- •Ibutilide
- •Procainamide
- •Quinidine
- •Methadone
- •Amiodarone hydrochloride
- •Arsenic trioxide
- •Cisapride
- •Calcium-channel blockers (e.g., lidoflazine)
- •Anti-infective agents (i.e., clarithromycin, erythromycin, halofantrine, pentamidine, or sparfloxacin)
- •Domperidone or droperidol
- •Antipsychotic agents (i.e., chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide)
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: belinostat (Drug)
结局指标
主要结局
Number of Confirmed Responses (Complete Response, Partial Response, or Hematologic Improvement) Noted on 2 Consecutive Evaluations at Least 4 Weeks Apart
时间窗: 12 weeks
Complete Response (CR) A CR is defined as a participant with bone marrow showing less than 5% myeloblasts with no evidence of dysplasia and with adequate peripheral blood counts for at least 2 months (hemoglobin \> 11 g/dl, neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3) and with no blasts in the peripheral. Partial Response (PR) All the CR criteria except bone marrow blasts decreased by ≥ 50% over pretreatment, or a less advanced WHO classification than pretreatment. Hematologic Improvement (HI) A 2g/dl increase in hemoglobin for participants with \<11g/dl hemoglobin at pretreatment, or an increase of \>30,000/mm\^3 platelets for participants with \<100,000/mm\^3 at pretreatment, or a 100% increase in neutrophil counts for participants with \<1500/mm\^3 at pretreatment
次要结局
- Time to Progression(Time from registration to the date of progression or last follow-up, assessed up to 3 years)
- Overall Survival(From date of registration to the date of last follow-up or death due to any cause, assessed up to 3 years)
- Duration of Response(From the date of documented response until the date of progression or last follow-up, assessed up to 3 years)
- Toxicity of Belinostat in Patients With Myelodysplastic Syndrome(Prior to each course (every 21 days), and every 3 months for up to 3 years after completion of study treatment)