NCT03009344已完成1 期
A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma
- •Participant who has measurable disease
- •Participant who had previous therapy with systemic chemotherapy and/or antibody therapy
- •Participant who had progressive disease (PD) or did not have a response (complete response [CR] or partial response [PR]) in previous systemic therapy, or relapsed or progressed after previous systemic therapy
- •Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Participant with life expectancy of ≥3 months from starting study drug administration
- •Participant with adequate renal, bone marrow, and liver function
- •Participant with left ventricular ejection fraction (LVEF) > 50%
- •Male and female participant ≥20 years of age at the time of informed consent
- •Participant who has provided written consent to participate in the study
排除标准
- •Participant with prior exposure to EZH2 inhibitor
- •Participant with a history or a presence of central nerves invasion
- •Participant with allogeneic stem cell transplantation
- •Participant with medical need for the continued use of potent or moderate inhibitors of CYP3A or P-gp, or potent or moderate inducer of CYP3A (including St. John's wort).
- •Participant with significant cardiovascular impairment
- •Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 milliseconds (msec)
- •Participant with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug
- •Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis
- •Participant with active infection requiring systemic therapy
- •Women of childbearing potential or man of impregnate potential who don't agree to use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later from last administration of study drug
- •Woman who are pregnant or breastfeeding
- •Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator
研究组 & 干预措施
Tazemetostat 800 mg
Experimental
Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days).
干预措施: Tazemetostat (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)
DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (\>) 7 days; 2) greater than or equal to (\>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) \>=Grade 3 nausea, vomiting, or diarrhea that persisted \>7 days despite maximal medical therapy; 6) \>=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted \>7 days; 7) Other Grade 3 toxicity lasting \>7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer \>=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.
次要结局
- T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- CL/F: Apparent Total Body Clearance of Tazemetostat(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days))
- Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the date of first dose up to 30 days after the last dose of study drug (up to 40 months))
- Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Fe: Fraction of Tazemetostat Dose Excreted in Urine(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- CLR: Renal Clearance of Tazemetostat(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days))
- AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State(Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387(Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days))
- Percentage of Participants With Objective Response(From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months))
研究者
研究点 (1)
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