A Phase 1 Clinical Trial to Evaluate Venetoclax With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Michael Choi
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose or biologically active dose.
研究概览
简要总结
The purpose of the study is to investigate whether the combination of venetoclax and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. If you agree, you will receive ibrutinib at a dose of up to 840 mg a day by mouth, as well as venetoclax. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.
详细描述
This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose (including doses higher than 420 mg) when combined with venetoclax
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
The primary safety endpoint is determination of DLTs during the first 35 days (completion of dose ramp up). The primary efficacy endpoint of overall response rate will be assessed on approximately Cycle 7, Day 1.
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
- •Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
- •Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in their treatment course.
- •Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study.
- •Adequate hematologic, hepatic and renal function
排除标准
- •Known CNS lymphoma or leukemia
- •History of Richter's or prolymphocytic transformation.
- •Primary ibrutinib resistance
- •Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
- •History of major surgery within 4 weeks prior to first dose on this study.
- •History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
- •Active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
- •Active hepatitis B or C infection.
- •Known history of infection with human immunodeficiency virus (HIV).
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- •History of stroke or intracranial hemorrhage within 6 months of first dose.
- •Requires anticoagulation with warfarin or other Vitamin K antagonists.
- •Requires treatment with a strong cytochrome P(CYP)450 3A inhibitor.
- •Pregnant or breast-feeding women
- •Current infection requiring parenteral antibiotics.
- •Active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification.
- •Patients who require immediate cytoreduction due to high risk of tumor lysis syndrome (ie, absolute lymphocyte count greater than 100k/uL).
研究组 & 干预措施
venetoclax with high-dose ibrutinib
venetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib.
干预措施: Venetoclax (Drug)
venetoclax with high-dose ibrutinib
venetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Maximum tolerated dose or biologically active dose.
时间窗: 1 year or more
Maximum tolerated dose or biologically active dose.
次要结局
- Progression free survival rate at completion of combination therapy(2 years or more)
- Stable disease rate(2 years or more)
- Overall response rate(2 years or more)
- Treatment-emergent adverse events(2 years or more)
研究者
Michael Choi
Clinical investigator
University of California, San Diego