A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- MEPD of single agent decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient
研究概览
简要总结
Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Valproic acid may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine together with valproic acid may be an effective treatment for non-Hodgkin's lymphoma. This phase I trial is studying the side effects and best dose of decitabine and valproic acid in treating patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.
详细描述
PRIMARY OBJECTIVES:
I. Determine the minimally effective pharmacological dose (MEPD) of single-agent decitabine in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.
II. Determine the maximum tolerated dose of valproic acid when administered with the MEPD of decitabine in these patients.
III. Determine the MEPD of valproic acid when administered with decitabine in these patients.
IV. Determine the toxic effects of decitabine alone and in combination with valproic acid in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 or cytologically confirmed aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:
- •Mantle cell lymphoma
- •Diffuse large cell lymphoma
- •Burkitt's lymphoma
- •Transformed NHL* arising from a previously diagnosed low-grade lymphoma, including any of the following:
- •Follicular lymphoma
- •Small lymphocytic lymphoma
- •Chronic lymphocytic leukemia
- •Relapsed or refractory disease
- •Relapsed or refractory disease must have occurred during the most recent prior therapy
- •Has accessible tissue for biopsy OR evidence of ≥ 50% bone marrow involvement AND willing to undergo serial biopsy
- •Not eligible for OR refused curative stem cell transplantation
- •No active or untreated CNS lymphoma
- •Performance status - ECOG 0-2
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 75,000/mm^3
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Bilirubin ≤ 1.5 mg/dL
- •Creatinine ≤ 2.0 mg/dL
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known HIV positivity
- •No ongoing or active infection
- •No other uncontrolled illness
- •No psychiatric illness or social situation that would preclude study compliance
- •Prior stem cell transplantation allowed
- •Recovered from all prior biologic therapy-related toxicity
- •Recovered from all prior chemotherapy-related toxicity
- •No other concurrent chemotherapy unless it is used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders
- •No concurrent corticosteroids unless they are used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders
- •Recovered from all prior radiotherapy-related toxicity
- •No concurrent palliative radiotherapy
- •Recovered from all prior therapy-related toxicity
- •No concurrent anticonvulsants, including valproic acid (except as used in this study)
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm II
Patients receive decitabine as in stage 1 and valproic acid PO TID on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: decitabine (Drug)
Arm II
Patients receive decitabine as in stage 1 and valproic acid PO TID on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: valproic acid (Drug)
Arm II
Patients receive decitabine as in stage 1 and valproic acid PO TID on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm II
Patients receive decitabine as in stage 1 and valproic acid PO TID on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MEPD of single agent decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient
时间窗: 28 days
MTD of valproic acid in combination with the MEPD of decitabine defined as the dose level below that dose at which greater than or equal to 2 DLT are observed and that results in less than or equal to 1 DLT in 6 patients using CTCAE v3.0
时间窗: 28 days
MEPD of valproic acid and decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient
时间窗: 28 days
Toxicities of single agent decitabine alone and in combination with valproic acid assessed using CTCAE v3.0
时间窗: Up to 3 years
次要结局
未报告次要终点