A Phase 1 Proof-of-Concept Study Investigating AZD6738 Monotherapy and Acalabrutinib in Combination With AZD6738 (ATR Inhibitor) in Subjects With Relapsed or Refractory High-risk Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 12
- 主要终点
- Number of participants experiencing dose-limiting toxicities
研究概览
简要总结
This study evaluates the safety, pharmacokinetics, pharmacodynamics and efficacy of acalabrutinib and ceralasertib (known as AZD6738) when taken in combination.
详细描述
This study is to determine the safety of ceralasertib when given as monotherapy (discontinued) and in combination with acalabrutinib in subjects with R/R CLL and in subjects who have few therapeutic options available to them. As such, this study includes a formal DLT assessment of the first 6-12 subjects dosed in Part 1 of the study. In addition, routine and regular safety monitoring will be undertaken during this study to fully assess safety of ceralasertib given as monotherapy and in combination with acalabrutinib, with toxicity assessment and dose reduction guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of relapsed or refractory CLL that meets published diagnostic criteria (International Workshop on Chronic Lymphocytic Leukemia [IWCLL] Hallek 2008) and supported/documented by medical records
- •Subjects must be Relapse/Refractory high risk CLL and have exhausted other therapeutic options according to local/regional standard of care
- •Must have received ≥1 prior therapy for treatment of their disease.
排除标准
- •A diagnosis of ataxia telangiectasia
- •Any prior exposure to an ATR inhibitor or known hypersensitivity to an excipient of the product.
- •Known history of infection with human immunodeficiency virus (HIV).
- •A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196 (acalabrutinib) and/or Ceralasertib
- •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- •Requirement of treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
- •Breast feeding or pregnant
研究组 & 干预措施
Arm B Part 1 and 2
ceralasertib + acalabrutinib in combination
干预措施: Ceralasertib (Drug)
Arm A Part 1 and 2
DISCONTINUED (ceralasertib monotherapy)
干预措施: Ceralasertib (Drug)
Arm B Part 1 and 2
ceralasertib + acalabrutinib in combination
干预措施: Acalabrutinib (Drug)
结局指标
主要结局
Number of participants experiencing dose-limiting toxicities
时间窗: 28 Days
Arm A (discontinued): When given as monotherapy in subjects with R/R high-risk CLL who have exhausted other therapeutic options according to local/regional standard of care. Arm B: Ceralasertib given in combination with acalabrutinib in subjects with R/R high-risk CLL who are suitable for treatment with a BTK inhibitor and ceralasertib, per investigator's clinical opinion.
次要结局
未报告次要终点