Phase 1b, Escalating Dose Study of AVL-292, a Bruton's Tyrosine Kinase (Btk) Inhibitor, as Monotherapy in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 113
- 试验地点
- 13
- 主要终点
- Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of AVL-292 as monotherapy in subjects with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM).
详细描述
Bruton's tyrosine kinase (Btk) is non-receptor tyrosine kinase with restricted cellular expression largely limited to B-lymphocytes, monocytes, and mast cells or basophils. Btk is a critical component of the B cell receptor (BCR) signaling network and is crucial for B cell development. Investigation has revealed that some B cell lymphomas and CLL depend on BCR signaling, suggesting that interruption of such signaling could be a promising therapeutic opportunity in B-NHL, CLL and WM.
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
- •Women and men ≥18 years of age
- •Body weight ≥50 kg.
- •Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop)
- •Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment.
- •Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months.
- •Ability to swallow oral capsules without difficulty
- •Has recovered from adverse toxic effects of prior therapies
- •Meet the following clinical laboratory requirements:
- •Creatinine ≤ 1.5 × upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 x ULN
- •AST and ALT ≤ 3 × ULN
- •Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's)
- •Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia)
- •Absolute Neutrophil count ≥ 1000/µL
排除标准
- •Prior allogeneic bone marrow transplant
- •Autologous stem cell transplant within 3 months of screening
- •Active central nervous system involvement
- •Subjects with autoimmune hemolytic anemia or immune thrombocytopenia
- •Prior treatment with a Btk inhibitor
- •Active uncontrolled infection
- •History of malabsorption
- •Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc.
- •History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months
- •History of another currently active cancer
- •History of major surgery within 4 weeks or minor surgery within 1 week
- •Other medical or psychiatric illness or organ dysfunction
- •HIV positive
- •Positive for Hepatitis B surface antigen or Hepatitis C-virus
研究组 & 干预措施
AVL-292
干预措施: AVL-292 (Drug)
结局指标
主要结局
Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.
时间窗: with in the first 28 days after initiation of once daily oral dosing
次要结局
- Establish recommended Phase 2 dose, after completing dose escalation in Part 1 and evaluating accumulated safety,PK,and PD data from the dose escalation phase (Part1)(Completion of Part 1 dose escalation phase of study)
- Evaluate the Pharmacokinetic parameters of AVL-292(First 28 days of dosing)
- Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk(First 28 days of dosing)
- Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM(After completion of 28 day cycle of treatment)