A Phase I/II, Multicenter, Open-Label, Nonrandomized Study to Evaluate the Tolerability and Safety of ASTX660 and the Efficacy at the Recommended Dose of ASTX660 in Patients With Relapsed or Refractory T-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results
研究概览
简要总结
Phase 1 (dose-escalation part): Investigate the tolerability and safety of ASTX660 in patients with r/r PTCL and r/r CTCL and determine the recommended dose (RD) for the Phase 2.
Phase 1 (ATLL expansion part): Evaluate the safety of ASTX660 at RD in patients with r/r ATLL.
Phase 2 : Evaluate the efficacy of ASTX660 at RD in patients with r/r PTCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with T-cell lymphoma with histological diagnosis based on WHO classification (2017)
- •Patients with evaluable lesions.
- •Patients with ECOG PS score of 0 or
- •Patients with adequate organ functions as shown below.
- •AST and ALT ≤ 2.0 × ULN (≤ 3.0 × ULN if liver infiltration is present)
- •Total bilirubin ≤ 1.5 × ULN
- •ANC ≥ 1,000/mm3 (≥ 750/mm3 if bone marrow infiltration is present)
- •Platelet count 50,000/mm3 (25,000/mm3 if bone marrow infiltration is present)
- •Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min
- •Amylase and lipase ≤ 1.0 × ULN
排除标准
- •Patients with active infection requiring treatment with antibiotics, antifungals, or antivirals
- •Patients with heart disease that meets the followings:
- •LVEF of < 50% by echocardiography or MUGA scan
- •Congestive heart failure (NYHA classification III or IV)
- •Uncontrolled heart disease including unstable angina pectoris or hypertension considered to require hospitalization within last 3 months (90 days)
- •Complete left bundle branch block, III degree (complete) atrioventricular block, use of pacemaker, history or complication of poorly controlled arrhythmia requiring treatment
- •History or complication of long QT syndrome
- •History or complication of ventricular arrhythmia requiring active treatment
- •Corrected QT interval of ≥ 470 msec based on 12-lead ECG performed at the screening
- •Concern on increased cardiac risk by participating in the study based on medical judgment
- •Patients receiving the following treatment for the primary disease prior to the initial dose of study drug
- •Chemotherapy or radiotherapy within last 3 weeks
- •Skin directed therapy including local treatment or phototherapy within last 3 weeks
- •Treatment with monoclonal antibody within last 4 weeks
- •Treatment with other study drugs or study treatment within last 3 weeks or 5 half-lives, whichever is longer
- •Patients with prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 14 weeks prior to the day of initial dose of study drug
- •Patients who have received corticosteroids at a dose exceeding a prednisone equivalent dose of 10 mg/day within 3 weeks prior to the initial dose of study drug.
- •Patients with Inadequately controlled diabetes mellitus
研究组 & 干预措施
Phase 1 dose-escalation part
Subjects with r/r PTCL and r/r CTCL will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, [7 days on/ 7 days off] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RD is determined.
干预措施: ASTX660 (Drug)
Phase 1 ATLL expansion part
Subjects with r/r ATLL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.
干预措施: ASTX660 (Drug)
Phase 2
Subjects with r/r PTCL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.
干预措施: ASTX660 (Drug)
结局指标
主要结局
Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results
时间窗: 28 days (Day1 to Day29)
Dose-limiting toxicities were defined as AEs occurring during this period that meet any of the following criteria, were not related to the primary disease, complication(s), or concomitant medication(s), and has a reasonable relationship with ASTX660. The Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) was used to determine severity. 1. Grade 4 thrombocytopenia, Grade 3 or higher clinically significant bleeding, or anemia requiring a new erythrocyte transfusion 2. Febrile neutropenia that does not resolve within 3 days or Grade 4 neutropenia that lasts for more than 7 days under appropriate treatment 3. Liver-associated abnormalities 4. Excepting the above AEs, any other Grade 3 or higher nonhematologic or Grade 4 hematologic toxicity except Grade 3 nausea, vomiting, or diarrhea lasting less than 48 hours
次要结局
- Pharmacokinetic Outcome of Concentration-time Curve (AUC)(Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose)
- Pharmacokinetic Outcome of Maximum Concentration (Cmax)(Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose)
- Pharmacokinetic Outcome of Time to Maximum Concentration (Tmax)(Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose)
- Pharmacokinetic Outcome of Elimination Half Life (t½)(Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose)
- Pharmacokinetic Outcome of Clearance of Drug From Plasma(Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose)