Multicohort Study to Customize Ibrutinib Treatment Regimens for Patients With Previously Untreated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 333
- 试验地点
- 74
- 主要终点
- Best Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of ibrutinib + venetoclax (I+V) and ibrutinib monotherapy regimens in which dosing of ibrutinib is either proactively reduced or reactively modified in response to adverse events (AEs).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 diagnostic criteria
- •For ibruinib + venetocIax (I+V) cohorts: eastern cooperative oncology group (ECOG) performance status of 0-
- •For ibrutinib monotherapy cohorts: ECOG performance status of 0-2
- •Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node greater than and equal to (>=) 1.5 centimeters (cm) in longest diameter
- •A participant using oral contraceptives must use an additional contraceptive method
- •A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or until 1 month after last dose or per local label if more conservative (for example, 3 months in European Union or Canada and 1 month in United States)
排除标准
- •Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as those participants with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study treatment, or the need for prednisone greater than (>) 20 milligrams (mg) daily (or corticosteroid equivalent) to treat or control the autoimmune disease
- •Known bleeding disorders (example, von Willebrand's disease or hemophilia)
- •Stroke or intracranial hemorrhage within 6 months prior to enrollment
- •Known or suspected Richter's transformation or central nervous system (CNS) involvement
- •Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class II, III, or IV congestive heart failure as defined by the New York Heart Association Functional Classification
研究组 & 干预措施
Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Participants will receive ibrutinib 420 mg capsule QD for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin and ibrutinib dose will be reduced to 280 mg and will be administered QD, venetoclax 400 mg tablets QD will be administered with ibrutinib 280 mg for 12 cycles through Cycle 15.
干预措施: Venetoclax (Drug)
Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Participants will receive ibrutinib 420 milligrams (mg) capsule every day (QD) for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin, and venetoclax 400 mg QD will be administered with ibrutinib 420 mg QD, orally for 12 cycles through Cycle 15.
干预措施: Venetoclax (Drug)
Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Participants will receive ibrutinib 420 mg capsule QD for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin and ibrutinib dose will be reduced to 280 mg and will be administered QD, venetoclax 400 mg tablets QD will be administered with ibrutinib 280 mg for 12 cycles through Cycle 15.
干预措施: Ibrutinib (Drug)
Cohort 2b: Continuous Ibrutinib Monotherapy
Participants will receive ibrutinib 420 mg QD for 1 cycle (1 cycle = 28 days) followed by Ibrutinib 280 mg QD (or last tolerated dose) and continue until disease progression or unacceptable toxicity.
干预措施: Ibrutinib (Drug)
Cohort 2a: Continuous Ibrutinib Monotherapy
Participants will receive ibrutinib 420 mg QD (or last tolerated dose) until disease progression (PD) or unacceptable toxicity.
干预措施: Ibrutinib (Drug)
Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Participants will receive ibrutinib 420 milligrams (mg) capsule every day (QD) for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin, and venetoclax 400 mg QD will be administered with ibrutinib 420 mg QD, orally for 12 cycles through Cycle 15.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Best Overall Response Rate (ORR)
时间窗: Up to 5 years
Best ORR is defined as the percentage of participants who achieve complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria as assessed by investigator.
次要结局
- Complete Response (CR) Rate(Up to 5 years)
- Duration of Response (DOR)(Up to 5 years)
- Progression Free Survival (PFS)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Cohorts 1a and 1b: Minimal Residual Disease (MRD) Negative Rate(Up to 5 years)
- Number of Participants with Adverse Events (AEs)(Up to 5 years)
- Number of Participants with AEs by Severity(Up to 5 years)
- Percentage of Participants with Rate of Discontinuation due to AEs(Up to 5 years)
- Percentage of Participants with Dose Reduction due AEs(Up to 5 years)
- Adherence Rates(Up to 5 years)
- Duration of Treatment(Up to 5 years)
- Time to Worsening as Measured by EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L)(Up to 5 years)
- Time to Worsening as Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30)(Up to 5 years)
- Time to Worsening as Measured by EORTC QLQ-CLL17(Up to 5 years)
- Time to Worsening as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score(Up to 5 years)