Phase II Study of Eltrombopag in Combination With Decitabine in Subjects With Advanced Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The goal of this clinical research study is to learn if eltrombopag given in combination with decitabine can help to control advanced MDS. The safety of this study drug combination will also be studied.
详细描述
Study Drug Administration:
Each cycle is 28 days.
If you are found to be eligible to take part in this study, you will receive decitabine by vein over 1 hour on Days 1-5 of each cycle.
You will also take eltrombopag capsules by mouth 1 time every day of each cycle. You should take it on an empty stomach (1 hour before a meal or 2 hours after a meal) with 8 ounces (1 cup) of water.
Do not eat calcium-rich foods (such as dairy products and juices with added calcium), or take other drugs (such as antacids) or supplements containing iron, calcium, aluminum, magnesium, selenium, and/or zinc for 4 hours before or 4 hours after taking eltrombopag.
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
- •Signed, informed consent must be obtained prior to any study specific procedures.
- •Subjects with a histologically confirmed diagnosis of MDS by FAB criteria, including both MDS and RAEB-T (AML with 20-30% blasts and multilineage dysplasia) and chronic myelomonocytic leukemia (CMML) with at least 10% bone marrow blasts by World Health Organization (WHO) classification are eligible.
- •Advanced MDS by virtue of intermediate-2 or high-risk MDS by IPSS score, or high or very-high risk by IPSS-R.
- •Platelet count </= 100 x 10^9/L at baseline
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Adequate liver function, as evidenced by a serum bilirubin </= 2x the ULN (except for patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST </= 3x the laboratory ULN.
- •Serum creatinine </= 2.5x upper limit of normal
- •Subjects must be >/= 18 years of age at the time of informed consent
- •Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subject) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following highly effective methods of contraception (i.e. Pearl index < 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study: - Complete abstinence from intercourse; - Intrauterine device (IUD); - Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide); - Male partner is sterile prior to entry into the study and is the only partner of the female; - Systemic contraceptives (combined or progesterone only).
排除标准
- •Subjects with any prior exposure to a thrombopoietin-receptor agonist
- •Prior hypomethylating agent treatment for MDS
- •Any prior or co-existing medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- •Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- •Active uncontrolled serious infection or sepsis at study enrollment
- •Clinically significant gastrointestinal disorders that may interfere with absorption of drug.
- •History of arterial thrombosis (i.e. stroke) in the past year
- •History of venous thrombosis currently requiring anti-coagulation therapy
- •Unstable angina, congestive heart failure (New York Heart Association (NYHA) > Class II), uncontrolled hypertension (diastolic blood pressure > 100mmHg), or recent (within 1 year) myocardial infarction
- •Subjects with a QTc > 480 msec (QTc > 510 msec for subjects with Bundle Branch Block) at baseline
- •Pregnant or breast-feeding
- •Subjects with known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), because eltrombopag is hepatically cleared, and underlying hepatic impairment may lead to an increased risk of hepatotoxicity. Eltrombopag has not been evaluated with combination antiretroviral regimens.
- •Subjects with liver cirrhosis (as determined by the investigator)
- •Subjects with hypersensitivity to study drugs or their excipients.
研究组 & 干预措施
Eltrombopag + Decitabine
Starting dose of Eltrombopag is 100 mg by mouth daily for each 28 day cycle. East Asians will start at 50 mg by mouth daily for each 28 day cycle.
Starting dose of Decitabine is 20 mg/m2 by vein on Days 1-5 for each 28 day cycle.
干预措施: Eltrombopag (Drug)
Eltrombopag + Decitabine
Starting dose of Eltrombopag is 100 mg by mouth daily for each 28 day cycle. East Asians will start at 50 mg by mouth daily for each 28 day cycle.
Starting dose of Decitabine is 20 mg/m2 by vein on Days 1-5 for each 28 day cycle.
干预措施: Decitabine (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 28 days
The primary endpoint is the overall response rate (ORR) based on the IWG-2006 criteria, which includes complete remission (CR), partial remission (PR), and hematologic improvement (HI).
次要结局
未报告次要终点