Phase I Study of Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Ruxolitinib
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with low or intermediate-1 risk MDS. The safety of this drug will also be studied, and whether it can help to control the disease.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3-6 participants will be enrolled in Part 1 of the study, and up to 7 participants will be enrolled in Part 2.
If you are enrolled in Part 1, the dose of ruxolitinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose of ruxolitinib. The second group of participants will receive the lowest dose of ruxolitinib for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. The third group of participants will receive the higher dose taken by the second group for 1 cycle and if no intolerable side effects are seen, the dose will be increased for Cycles 2 and beyond. The fourth group of participants will take the higher dose taken by the third group for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond.
If you are enrolled in Part 2, you will receive ruxolitinib at the highest dose that was tolerated in Part 1.
Study Drug Administration:
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
- •Patients with previously treated low or intermediate-1 risk MDS by the IPSS classification (this is defined in table 1)
- •Patients must have one of the following: elevated b2-microglobulin levels (defined as 2 times compared to normal), carry a JAK2 mutation, or presence of phosphorylated p65 NF-kB component in at least 5% of bone marrow cells.
- •Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
- •Age >/= 18 years old
- •Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or other investigational agents are allowed. A four week wash out period will be required before receiving study medication.
- •Patients must have the following non-hematologic values Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 2.5 x Upper Limit of Normal (ULN) or </= 5.0 x ULN if hepatic involvement is present; Serum bilirubin </= 2 x ULN; Serum creatinine </= 2 x ULN or 24-hour creatinine clearance >/= 60 ml/min
- •Patients with Childbearing potential must agree to use appropriate forms of birth control
排除标准
- •Previously untreated low or intermediate-1 risk MDS patients because there are approved therapies for these patients.
- •Uncontrolled undercurrent illness that in the opinion of the treating physician would contraindicate the use of the drug.
- •Patients with active infections including uncontrolled HIV infection, active hepatitis B, C, or any other symptomatic systemic infection requiring active therapy will be excluded from study
- •Patients receiving potent CYP3A4 (such as but not limited to boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) inhibitors will be excluded from the study.
- •Women who are pregnant or lactating.
- •Patients with a white blood cell count of more than 30x10^3 K/uL will not be eligible for this study.
- •Patients that have received prior allogeneic stem cell transplantation are excluded from this study.
研究组 & 干预措施
Ruxolitinib
Part 1: Dose of ruxolitinib received will depend when patient joined study. The first group of patients receive the lowest dose of ruxolitinib. Starting dose level for Part 1, 5 mg by mouth twice a day for a 28 day cycle. The second group of patients receive the lowest dose of ruxolitinib for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. The third group of patients receive the higher dose taken by the second group for 1 cycle and if no intolerable side effects are seen, the dose will be increased for Cycles 2 and beyond. The fourth group of patients take the higher dose taken by the third group for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond.
If patients enrolled in Part 2, they will receive ruxolitinib at the highest dose that was tolerated in Part 1.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Ruxolitinib
时间窗: 28 days
Maximum tolerated dose (MTD) is the maximum dose at which \<33% of patients experience a dose limiting toxicity (DLT). Dose limiting toxicity defined as any grade 3 or higher non-hematologic toxicity.
次要结局
- Number of Participants with Response of Ruxolitinib(8 weeks)