NCT01029509终止1 期
An Open-label, Non-randomized Study to Assess the Pharmacokinetics, Dose Limiting Toxicity and Maximum Tolerated Dose of OPB-31121 in Subjects With Advanced Leukemias or Myelodysplastic Syndromes
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of OPB-31121 that can be given to patients with leukemia or myelodysplastic syndrome (MDS).
详细描述
The Study Drug:
In studies that have been performed in animals, OPB-31121 has been shown to stop certain changes to proteins in the body. Stopping these changes may have an effect on tumor cells. How OPB-31121 works is not fully known.
Study Groups:
The first 3 participants enrolled in the study will receive the lowest level of OPB-31121. Each additional group of 3 or 4 participants will receive a dose level dependent upon how the previous group responded to the study drug.
You may have up to 13 study "cycles" (about 273 days). During each 28 day study cycle, you will receive the study drug for 21 days and then "rest" (no study drug) for 7 days. The cycle is 28 days, 21 days of drug, 7 days of rest.
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
- •Subjects with a diagnosis of treatment resistant or relapsed AML, ALL, or CLL for whom no standard treatment therapies are expected to result in durable remission. Subjects with advanced MDS should have failed lenalidomide or a hypomethylating agent. Subjects with CLL should have failed or relapsed after prior fludarabine and Campath. Subjects with CML should have previously exhausted standard therapy which provides clinical benefit. In addition, untreated subjects not eligible for standard therapy or unwilling to receive standard therapy with the above diagnosis will be eligible.
- •Male and female subjects > / = 18 years of age
- •Male and female subjects who are surgically sterile (ie, have undergone orchidectomy or hysterectomy, respectively); female subjects who have been postmenopausal for at least 24 consecutive months; or male and female subjects who agree to remain abstinent or to begin two acceptable methods of birth control from one week prior to drug administration through 30 days (for females) and 90 days (for males) from the last dose of study medication.
- •(continued from #3) If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), condom, diaphragm, cervical cap or sponge with spermicide.
- •Adequate liver function defined as </= 2.5 * institutional upper limit of normal (ULN), </= 2.5 * institutional ULN for alanine transaminase (ALT), aspartate transaminase, (AST) and bilirubin within normal limits unless Gilbert disease has been documented. .
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •In the absence of rapidly proliferative disease, a minimum of 2 weeks should elapse since prior standard or experimental therapy. Subjects must have recovered to grade less than or equal to 1 from any prior nonhematologic toxicities associated with any previous treatments. Use of leukopheresis or hydrea up to 48 hrs prior to the start of the study will be allowed in presence of proliferative disease. Use of hydrea will be permitted up to 5 days in each cycle for the control of proliferative disease.
- •All eligible subjects must have received prior therapy (including chemotherapy, radiation therapy or surgery) greater than or equal to 2 weeks prior to study entry (Screening) and have recovered to Grade 1 toxicity from any prior non-hematological toxicity and to Grade 2 toxicity from any prior hematological toxicity except for thrombocytopenia defined as Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding following investigator's assessment of causality and positive relationship to study medication before participation in this trial.
- •For CLL subjects only, all subjects with Rai Stages III-IV are eligible. For subjects with Rai stage 0-I disease, one or more indications for treatment as defined by the NCI sponsored Working Group must exist: • Massive or progressive splenomegaly; OR • Massive lymph nodes; nodal clusters, or progressive lymphadenopathy; OR • Grade 2 or 3 fatigue; or fever > / = 100.5° F or night sweats for greater than 2 weeks without documented infection; or presence of weight loss > / = 10% over the preceding 6 months;
- •(continued from #9) OR • Progressive lymphocytosis with an increase in lymphocyte count of > / = 50% over a 2- month period or an anticipated doubling time of less than 6 months.
- •For CML, subjects who have exhausted standard therapy which provides clinical benefit.
- •Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the study.
- •Subjects must have a life expectancy of > 3 months.
- •Subjects must have a normal ejection fraction (>/= 50%) as measured by multiple gated acquisition (MUGA) scan.
- •Subjects must have a normal serum creatinine (at baseline only) with a measured 24 hour creatinine clearance of > 60 cc/min.
排除标准
- •Clinically significant condition in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the subject at risk or interfere with outcome variables.
- •Subjects with active central nervous system (CNS) involvement by leukemia. Subjects with prior history of CNS disease will qualify if active disease is ruled out by imaging studies or spinal tap
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Subjects having taken an investigational drug or therapy within 14 days prior to dosing.
- •Subjects who are pregnant or breast feeding. A negative serum pregnancy test must be confirmed prior to the first dose of study medication for WOCBP.
- •Use of CYP3A4-enzyme inhibiting drugs and food; use of CYP3A4-enzyme inducing drugs and food; use of CYP2C9-enzyme inhibiting drugs; and use of CYP2C9 enzyme inducing drugs. Others: propranolol, lidocaine, propafenone, verapamil, nitroglycerin, and midazolam.
- •Subjects with history of coagulopathy (or taking anticoagulants) including deep vein thrombosis (DVT)/ PE, unstable angina, myocardial infarction and stroke within the last 6 months.
研究组 & 干预措施
OPB-31121
Experimental
OPB-31121 200 mg twice daily for 21 days followed by 7 days of rest
干预措施: OPB 31121 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Assessed at end of 28 day cycle for each dose cohort
MTD defined as highest dose level at which \< 2 of 6 subjects experience dose limiting toxicity (DLT) during the first cycle.
次要结局
未报告次要终点
研究者
研究点 (1)
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