NCT00351975已完成1 期
A Phase I Study of PXD101 in Combination With Azacitidine (5-Aza) for Advanced Hematologic Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose of belinostat in combination with azacitidine
研究概览
简要总结
This phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases. 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. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving belinostat together with azacitidine may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of PXD101 (belinostat) when given in combination with azacitidine (when azacitidine is utilized at a dose range where its effects on cellular differentiation are known to be predominant) in patients with advanced hematologic cancers or other diseases.
SECONDARY OBJECTIVES:
I. Identify any additive or synergistic effects of this regimen on pharmacodynamic parameters, including apoptosis and re-expression of specific target genes.
II. Assess any evidence of clinical activity (complete remission, partial remission, hematologic improvement, stable disease) of this regimen in these patients.
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
- •Histologically confirmed diagnosis of 1 of the following:
- •Relapsed or refractory acute myeloid leukemia (AML)
- •Relapsed or refractory acute promyelocytic leukemia (must have failed both tretinoin and arsenic trioxide)
- •Relapsed or refractory acute lymphoblastic leukemia
- •Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes (MDS) or myeloproliferative disorders, OR therapy-related AML
- •Chronic myelogenous leukemia in accelerated or blast phase
- •Advanced phases of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders, as defined by ≥ 1 of the following:
- •Presence of anemia (hemoglobin < 10 g/dL and/or red blood cell transfusion dependent)
- •Presence of palpable splenomegaly
- •MDS, including chronic myelomonocytic leukemia
- •Must have intermediate or high-risk International Prognostic Scoring System (IPSS) scores (≥ 0.5)
- •Low-risk IPSS scores allowed provided ≥ 1 of the following criteria are met:
- •Hemoglobin < 10 g/dL and/or red blood cell transfusion dependent
- •Platelet count < 50,000/mm³
- •Absolute neutrophil count < 1,000/mm³
- •Refractory disease OR no standard therapy exists
- •Evidence of AML associated with dysplasia on bone marrow histology for elderly patients (i.e., > 60 years old) who are previously untreated and not candidates for or unwilling to undergoing induction therapy
- •No known active CNS involvement with disease
- •CALGB performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
- •ALT ≤ 3 times upper limit of normal (unless due to disease)
- •Creatinine ≤ 2 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 or Azacitidine
- •No history of allergic reactions to mannitol
- •No history of dose-limiting toxicity during prior treatment with Azacitidine
- •No concurrent uncontrolled illness including, but not limited to, the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situation that would preclude compliance with study requirements
- •No marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 500 msec)
- •No long QT syndrome
- •No uncontrolled cardiovascular disease, including the following:
- •Severe uncontrolled hypertension
- •Uncontrolled congestive heart failure related to primary cardiac disease
- •Uncontrolled cardiac arrhythmia
- •Uncontrolled ischemic or severe valvular heart disease
- •Myocardial infarction within the past 6 months
- •See Disease Characteristics
- •Recovered from prior therapy
- •At least 2 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
- •At least 2 weeks since prior radiotherapy
- •At least 4 weeks since prior investigational agents
- •At least 24 hours since prior hydroxyurea
- •At least 2 weeks since prior valproic acid
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- 另有 3 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (chemotherapy)
Experimental
Patients receive azacitidine SC on days 1-5.
干预措施: Azacitidine (Drug)
Arm I (chemotherapy)
Experimental
Patients receive azacitidine SC on days 1-5.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (chemotherapy, enzyme inhibitor therapy)
Experimental
Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.
干预措施: Belinostat (Drug)
Arm II (chemotherapy, enzyme inhibitor therapy)
Experimental
Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.
干预措施: Azacitidine (Drug)
Arm II (chemotherapy, enzyme inhibitor therapy)
Experimental
Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Maximum tolerated dose of belinostat in combination with azacitidine
时间窗: Course 1 (28 days)
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 or 4.0.
次要结局
- Association of methylation status, categorized as positive or negative, with changes in target gene expression(Baseline, days 4 or 5, and days 25-28)
- Clinical activity (complete remission, partial remission, stable disease, hematologic improvement)(After 4, 8, and 16 weeks)
- Changes in pharmacodynamic variables (target gene expression, apoptosis)(Course 1 (baseline to day 5))
研究者
研究点 (4)
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