A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 319 in Adult Subjects With Relapsed or Refractory Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs
研究概览
简要总结
This is a multi-center, phase 1, open-label first-in-human study of AMG 319 in subjects with relapsed or refractory lymphoid malignancies. This study consists of two parts. The dose exploration in part 1, studies cohorts of 3 subjects with relapsed or refractory lymphoid malignancies and uses a practical continuous reassessment model [CRM] to guide dose escalation and to define the MTD. The dose expansion in part 2 will enroll 20 subjects with CLL at a dose no higher than the MTD and further explore the safety, PK, and clinical activity of AMG 319 in this patient population.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1 (Dose Exploration): Relapsed or refractory lymphoid malignancy of the following type for which standard treatment does not exist or is no longer effective:
- •B-cell Chronic Lymphocytic Leukemia (CLL) confirmed by immunophenotype or Non-Hodgkin Lymphoma: Low or intermediate grade B-cell NHL, mantle cell lymphoma, non-cutaneous T-cell NHL confirmed by histology and/or immunophenotype
- •Part 2 (Dose Expansion): Subjects must have relapsed or refractory B-cell Chronic Lymphocytic Leukemia confirmed by immunophenotype for which standard treatment does not exist or is no longer effective.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- •Life expectancy of > 3 months, in the opinion of the investigator
- •Men or women ≥ 18 years old
- •Hematological function, as follows:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (unless due to disease-related bone marrow involvement as documented by bone marrow biopsy, ≥ 0.5 x 109/L) Platelet count ≥ 50 x 109/L (without a transfusion within 14 days before enrollment) Hemoglobin ≥ 9 g/dL
- •Hepatic function, as follows: Aspartate aminotransferase (AST) < 3.0 x ULN Alanine aminotransferase (ALT) < 3.0 x ULN Alkaline phosphatase (ALP) < 2.0 x ULN (< 5 x ULN in subjects whom the PI and sponsor agree that clinical data suggest an extrahepatic source of elevation) Total bilirubin < 1.5 x ULN (< 3.0 x ULN for subjects with documented Gilbert's Disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation) Amylase ≤ 2.0 x IULN Lipase ≤ 2.0 x IULN
排除标准
- •Primary or disseminated tumor involving the central nervous system (CNS)
- •A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years
- •History of allogeneic stem-cell (or other organ) transplantation
- •Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome
- •QTcF interval > 470 msec
- •Active or chronic hepatitis B or hepatitis C infection, determined by serologic tests
- •Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment
研究组 & 干预措施
Part II Dose Expansion
Dose selected from Part I dose exploration
干预措施: AMG 319 (Drug)
Part I Dose Exploration
The AMG 319 doses proposed for this study are 25, 50, 100, 200, 300 and 400 mg administered by mouth once daily.
干预措施: AMG 319 (Drug)
结局指标
主要结局
Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs
时间窗: 28 Days after last subject enrolled per each cohort
Treatment-emergent adverse events
时间窗: 28 Days after last subject enrolled per each cohort
PK parameters
时间窗: 28 Days after last subject enrolled per each cohort
Clinical/radiological response rate for CLL subjects
时间窗: With primary analysis
次要结局
- Phospho-AKT level in circulating CLL cells(With primary analysis)
- Number of patients with clinical/radiological response(With primary analysis)