The MAVRiC Study: A Phase II Study of Disease Risk Mutation Guided Finite Duration Acalabrutinib Plus Venetoclax for Relapse in CLL/SLL After First-line Finite Covalent BTKi Plus BCL2i Combination, With or Without Obinutuzumab
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 80
- 试验地点
- 41
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, and have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.
详细描述
The purpose of this study is to explore the use of second line (2L) treatment with AV after relapse following first line (1L) cBTKi + BCL2i by assessment of ORR in participants with CLL/SLL. This study will generate efficacy and safety data needed to understand outcomes associated with AV in patients who initially responded with partial remission (PR) or better for a minimum of 2 years from the end of 1L cBTKi + BCL2i combination treatment and are experiencing clinical relapse requiring further treatment. MAVRiC explores AV as second-line (2L) CLL/SLL treatment after relapse on first-line (1L) cBTKi + BCL-2 by assessment of overall response rate (ORR)
- The study duration for each participant will be up to 5 year.
- The study consists of screening, treatment, and post-intervention follow-up periods.
- Participants will be grouped into low or high risk cohorts based on disease risk determined by IGHV mutation and TP53 aberrancy.
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Participant must be ≥ 18 years at the time of signing informed consent.
- •Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
- •Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.
- •The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:
- •IGHV (mutated vs. unmutated)
- •del(17p) (present or absent)
- •TP53 mutation (present or absent)
- •ECOG performance status 0, 1 or 2
- •Adequate organ and bone marrow (BM) function.
排除标准
- •Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
- •Significant cardiovascular or cerebrovascular disease.
- •Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
- •Child-Pugh B/C liver cirrhosis.
- •History of prior or current malignancy.
- •HIV positive
- •History of progressive multifocal leukoencephalopathy (PML).
- •Active hepatitis B or C infection:
- •Corticosteroid use > 20 mg within 1 week before the first dose of study intervention.
- •History of hypersensitivity or anaphylaxis to study intervention(s).
- •Requires treatment with a strong CYP3A4 inhibitor/inducer.
- •Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- •Major surgical procedure within 30 days of the first dose of study intervention.
研究组 & 干预措施
Acalabrutinib and Venetoclax
For Cohort 1, each participant will be in the study for approximately 5 years (60 months) counting from C1D1, starting with 2 cycles of acalabrutinib lead-in treatment, followed by 12 cycles of AV combination treatment, and 4 years of follow-up.
For Cohort 2, each participant will be in the study for approximately 5 years (60 months) counting from C1D1 starting with 2 cycles of acalabrutinib lead-in treatment, followed by 22 cycles of AV combination treatment, and 3 years of follow-up.
干预措施: Acalabrutinib (Drug)
Acalabrutinib and Venetoclax
For Cohort 1, each participant will be in the study for approximately 5 years (60 months) counting from C1D1, starting with 2 cycles of acalabrutinib lead-in treatment, followed by 12 cycles of AV combination treatment, and 4 years of follow-up.
For Cohort 2, each participant will be in the study for approximately 5 years (60 months) counting from C1D1 starting with 2 cycles of acalabrutinib lead-in treatment, followed by 22 cycles of AV combination treatment, and 3 years of follow-up.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14
ORR, defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per iwCLL criteria as assessed by the investigator.
次要结局
- Progression Free Survival (PFS)(PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days))
- Duration of Response (DoR)(DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days))
- Event Free Survival (EFS)(EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days))
- Overall Survival (OS)(OS will be assessed every 3 months through the study completion, for 5 years)
- Time to Next Treatment (TTNT)(TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days))
- Rate of undetectable Minimal Residual Disease (uMRD)(uMRD will be measured at 3 months after last treatment)
- Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i(Safety and tolerability will be evaluated throughout the study for 5 years)