Evaluation of Ruxolitinib and Pracinostat Combination as a Therapy for Patients With Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The goal of this clinical research study is to learn if pracinostat, when given in combination with ruxolitinib, can help to control myelofibrosis (MF). The safety of this drug combination will also be studied.
This is an investigational study. Pracinostat is not FDA-approved or commercially available. It is currently being used for research purposes only. Ruxolitinib is FDA-approved and commercially available to treat MF.
The study doctor can explain how the study drugs are designed to work.
Up to 25 participants will be enrolled in this study. All will take part at MD Anderson.
详细描述
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take ruxolitinib by mouth 2 times each day. You may take your dose of ruxolitinib with or without food.
You will also take pracinostat by mouth 1 time each day for 3 alternating days (for example Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) every 3 weeks starting on Day 1 of Cycle 4. You will take your dose of pracinostat in the morning, about 30 minutes before or 2 hours after a meal. You should swallow your dose of pracinostat whole with a cup of water (about 8 ounces).
You will be given a study drug diary to write down when you take your dose of study drugs and if you miss or vomit any doses of study drug. You must bring the diary with you to the clinic on Day 1 of each cycle and at the end-of-treatment visit. You will also need to bring any leftover pills and any empty containers of the study drugs to the clinic when the study doctor tells you to do so.
Study Visits:
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
- •Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS).
- •Palpable splenomegaly of more than or equal to 5 cm below left costal margin on physical exam
- •Understanding and voluntary signing an Institutional Review Board (IRB)-approved informed consent form.
- •Age equal to or more than 18 years at the time of signing the informed consent.
- •Disease-free of other malignancies.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Negative pregnancy test in females of childbearing potential (FCBP). Male patients with female partners of child-bearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Acceptable forms of contraception include 1 highly effective method such as an intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or partner's vasectomy and at least 1 additional approved barrier method such as a latex condom, diaphragm, or cervical cap. Female patients of childbearing potential must not be breast-feeding or planning to breast feed and must have a negative pregnancy test ≤7 days before first study treatment.
- •QTcF interval equal to or less than 470 msec
- •Normal serum potassium magnesium levels
- •Adequate organ function as demonstrated by the following: Direct bilirubin equal to or less than 2.0 mg/dL, Serum creatinine equal to or less than 2.0 mg/dL., Alanine transaminase (SGPT) equal to or less than 3 x upper limit of normal (unless considered to be related to MF or patient has known history of Gilberts)
- •Platelets >/= 50000/uL
- •Absolute Neutrophil count (ANC) >/= 1000/uL
排除标准
- •Prior therapy with a JAK inhibitor (other than ruxolitinib for less than 3 months duration and currently on it) or HDACi. Patients that are currently on ruxolitinib for less than 3 months of therapy are eligible.
- •Use of any other standard or experimental therapy within 14 days of starting study therapy.
- •Lack of recovery from all toxicity from previous therapy to grade 1 or baseline.
- •Suspected pregnancy, pregnant or lactating females.
- •Any condition, including the presence of laboratory abnormalities, which in the opinion of the treating physician places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Known positive for HIV or infectious hepatitis, type A, B or C.
- •Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
- •Cardiopulmonary function criteria: • Current unstable arrhythmia requiring treatment • History of symptomatic congestive heart failure • History of myocardial infarction within 6 months of enrollment • Current unstable angina • Family history of long QT syndrome
研究组 & 干预措施
Ruxolitinib + Pracinostat
Ruxolitinib starting dose 15 mg orally twice/day in 28-day cycle (dose assigned based on platelet count, if low platelet count gradual up-titration from a starting dose of 5 mg) - given alone for first 3 months, then Pracinostat added at starting dose 60 mg orally once/day for 3 alternating days every 3 weeks starting Day 1 of Cycle 4.
Dose of Ruxolitinib may be increased or decreased prior to initiation of Pracinostat. Quality of Life Questionnaire.
干预措施: Ruxolitinib (Drug)
Ruxolitinib + Pracinostat
Ruxolitinib starting dose 15 mg orally twice/day in 28-day cycle (dose assigned based on platelet count, if low platelet count gradual up-titration from a starting dose of 5 mg) - given alone for first 3 months, then Pracinostat added at starting dose 60 mg orally once/day for 3 alternating days every 3 weeks starting Day 1 of Cycle 4.
Dose of Ruxolitinib may be increased or decreased prior to initiation of Pracinostat. Quality of Life Questionnaire.
干预措施: Pracinostat (Drug)
Ruxolitinib + Pracinostat
Ruxolitinib starting dose 15 mg orally twice/day in 28-day cycle (dose assigned based on platelet count, if low platelet count gradual up-titration from a starting dose of 5 mg) - given alone for first 3 months, then Pracinostat added at starting dose 60 mg orally once/day for 3 alternating days every 3 weeks starting Day 1 of Cycle 4.
Dose of Ruxolitinib may be increased or decreased prior to initiation of Pracinostat. Quality of Life Questionnaire.
干预措施: Questionnaire (Behavioral)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 3 months
Objective response rate (ORR), defined as a clinical improvement (CI), partial remission (PR), and complete remission (CR) according to the International Working Group (IWG) Criteria. Complete remission (CR): bone marrow blasts \<5%, hemoglobin \>/= 10, absolute neutrophil count (ANC) \>/= 1000, platelets \>/= 100, \<2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin \>/= 8.5 but \< 10, \<2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly \>/= 50%, \>/=50% reduction in MPN-SAF TSS
次要结局
- Toxicity of Combination of Ruxolitinib With Pracinostat(3 months)