A Phase I Study of Carfilzomib in Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Determine safety of carfilzomib by evaluating the toxicity profile.
研究概览
简要总结
RATIONALE:
Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE:
This phase I trial is studying the side effects and the best dose of carfilzomib in treating patients with relapsed or refractory chronic lymphocytic leukemia(CLL),small lymphocytic lymphoma(SLL), or prolymphocytic leukemia (PLL).
详细描述
PRIMARY OBJECTIVES:
I. To determine the dose limiting toxicity (DLT) and maximal tolerated dose (MTD) of carfilzomib in patients with relapsed or refractory Chronic Lymphocytic Leukemia(CLL) / Small Lymphocytic Lymphoma (SLL) and Prolymphocytic Leukemia (PLL).
II. To evaluate the safety and toxicity profile of carfilzomib in relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL).
SECONDARY OBJECTIVES:
I. To evaluate efficacy of carfilzomib therapy in relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL) to justify future phase II studies.
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
- •Previously treated patients with a diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or prolymphocytic leukemia (PLL) by NCI Criteria with intermediate or high risk B-Cell chronic lymphocytic leukemia (CLL)(Modified Rai stage) satisfying at least one of the criteria for active disease requiring treatment;patients with a history of Richter's transformation are eligible if they now have evidence of chronic lymphocytic leukemia (CLL) only, with < 10% large cells in the bone marrow
- •Massive or progressive splenomegaly and/or lymphadenopathy; or need for cytoreduction for stem cell transplant
- •Anemia (hemoglobin < 11 g/dl) or thrombocytopenia (platelets < 100 x 10^9/L)
- •Presence of weight loss > 10% over the preceding 6 month period
- •NCI grade 2 or 3 fatigue
- •Fevers > 100.5 °C or night sweats for greater than 2 weeks without evidence of infection
- •Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months
- •Creatinine Clearance (CrCl) > 15mL/min
- •Alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
- •Bilirubin =< 2 times the upper limit of normal, unless disease related
- •Platelets >= 20 x 10^9/L and absence of active bleeding
- •Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status =< 2
- •Patients must not have secondary cancers that result in a life expectancy of <2 years or that would confound assessment of toxicity in this study
- •Patients of all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined-
- •Patients must provide written informed consent
排除标准
- •Absence of previously treated chronic lymphocytic leukemia (CLL)
- •Female subject that is pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception prior to study entry, duration of study participation,and 30 days following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
- •Patients with congestive heart failure (CHF)in whom pre-treatment hydration would be prohibitive;New York Heart Association (NYHA) Class III/IV CHF is excluded
- •Patients who have had treatment for chronic lymphocytic leukemia (CLL) within 2 weeks, although palliative steroids are acceptable
- •Patient unable to give written informed consent
- •Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1
- •Patients with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics or antivirals are acceptable
- •Patients who have previously taken bortezomib
研究组 & 干预措施
Arm 1
Patients receive carfilzomib IV over 30 minutes once daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Performance of pharmacology, pharmacodynamic and pharmacogenomic studies allow assessment of carfilzomib mechanism of action and also to understand how the variability of these different features correlate with clinical benefit/response and also toxicity.
干预措施: carfilzomib (Drug)
Arm 1
Patients receive carfilzomib IV over 30 minutes once daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Performance of pharmacology, pharmacodynamic and pharmacogenomic studies allow assessment of carfilzomib mechanism of action and also to understand how the variability of these different features correlate with clinical benefit/response and also toxicity.
干预措施: Cytokine Assessment (Other)
Arm 1
Patients receive carfilzomib IV over 30 minutes once daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Performance of pharmacology, pharmacodynamic and pharmacogenomic studies allow assessment of carfilzomib mechanism of action and also to understand how the variability of these different features correlate with clinical benefit/response and also toxicity.
干预措施: Pharmacodynamic Studies (Other)
Arm 1
Patients receive carfilzomib IV over 30 minutes once daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Performance of pharmacology, pharmacodynamic and pharmacogenomic studies allow assessment of carfilzomib mechanism of action and also to understand how the variability of these different features correlate with clinical benefit/response and also toxicity.
干预措施: Proteosome Inhibition Assessment (Other)
Arm 1
Patients receive carfilzomib IV over 30 minutes once daily on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Performance of pharmacology, pharmacodynamic and pharmacogenomic studies allow assessment of carfilzomib mechanism of action and also to understand how the variability of these different features correlate with clinical benefit/response and also toxicity.
干预措施: Pharmacogenomic Studies (Other)
结局指标
主要结局
Determine safety of carfilzomib by evaluating the toxicity profile.
时间窗: Up to 24 months
The safe use of carfilzomib will be assessed by: * Determining the dose limiting toxicity and maximal tolerated dose of carfilzomib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) and prolymphocytic leukemia (PLL) * To evaluating the toxicity profile of carfilzomib in relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) and prolymphocytic leukemia (PLL)
次要结局
- To evaluate the efficacy of Carfilzomib therapy in relapsed or refractory chromic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL)(Up to 24 months)
研究者
Jennifer Woyach
Principal Investigator
Ohio State University Comprehensive Cancer Center