A Phase II Study of Depsipeptide, a Histone Deacetylase Inhibitor, in Relapsed or Refractory Mantle Cell or Diffuse Large Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment
研究概览
简要总结
FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
I. Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma.
II. Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients.
III. Determine 2-year progression-free and overall survival.
OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.
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 aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:
- •Mantle cell lymphoma
- •Diffuse large cell lymphoma
- •(Ineligible for or unwilling to undergo stem cell transplantation)
- •Relapsed or refractory disease:
- •Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation
- •No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease
- •Measurable disease, defined as >= 1 lesion >= 1.5 cm in the longest diameter
- •No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma)
- •ECOG performance status 0-2
- •Absolute neutrophil count >= 1,000/mm^3 OR >= 500/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
- •Platelet count >= 75,000/mm^3 OR >= 50,000/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
- •Bilirubin normal
- •Alkaline phosphatase =< 2 times upper limit of normal (ULN)
- •AST =< 2 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure
- •No history of serious ventricular arrhythmia
- •QTc < 500 msec
- •No evidence of cardiac hypertrophy on ECG
- •No known HIV positivity
- •No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes)
- •Recovered from prior therapy
- •No prior doxorubicin hydrochloride >= 450 mg/m^2 or mitoxantrone >= 112 mg/m^2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" < 450 mg/m^2
- •No prior therapy with a histone deacetylase inhibitor
- •No concurrent dexamethasone or prednisone except for refractory nausea/vomiting
- •No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate)
- •Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic)
- •No CNS lymphoma
- •Creatinine normal
- •Cardiac function >= 50% by MUGA
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.
干预措施: romidepsin (Drug)
结局指标
主要结局
Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment
时间窗: 24 weeks (6 courses of 4 week cycles)
International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen.
次要结局
- Median Progression Free-survival (PFS)(2 Years)
- Median Overall Survival(5 Years)