A Phase 2 Trial of Zanubrutinib and Venetoclax in Previously Treated CLL/SLL Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- Rate of undetectable minimal residual disease (uMRD)
研究概览
简要总结
This study is being done to test the effectiveness of zanubrutinib in combination with venetoclax in participants with previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
详细描述
This is an open-label, non-randomized phase 2 trial assessing the combination of zanubrutinib and venetoclax in adult participants with CLL or SLL who have relapsed after at least one prior therapy.
Participants will receive study treatment for 15 months initially. There is an option for an additional 12 months of re-treatment with study therapy at the time of disease recurrence. Participants will be followed for 36 months after they discontinue the study drugs.
The study will enroll up to 45 participants. BeiGene Ltd. is providing funding for the trial and the study drug zanubrutinib.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Known BTK C481X mutation.
- •For enrollment to Cohort B: participants who have received prior treatment with both a BTK inhibitor and BCL-2 inhibitor.
- •Participants who have had previous anti-cancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy, biologic therapy, hormonal therapy, surgery, investigational agents, and/or tumor embolization) within 2 weeks of Cycle 1 Day 1 with the following exceptions:
- •Hormonal therapy given in the adjuvant setting
- •Corticosteroid therapy (prednisone or equivalent ≤ 20 mg daily) is allowed as clinically warranted as long as the dose is stabilized at least for 7 days prior to initial dosing. Topical, inhaled, intra-articular, or ophthalmologic corticosteroids are permitted
- •Participants enrolling to Cohort C may remain on prior BTK inhibitor therapy up until 2 days prior to Cycle 1 Day 1
- •History of a prior allogeneic hematologic stem cell transplant.
- •Participants with known central nervous system (CNS) involvement, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with no known history of CNS involvement are not required to undergo CT scan or lumbar puncture (LP) for trial eligibility unless the participant is symptomatic as judged by the treating investigator.
- •Participants who are receiving any other investigational agents at the time of study entry.
- •History of other malignancies, with the following exceptions:
- •Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease
- •Low-risk prostate cancer on active surveillance
- •Participants who have been vaccinated with live, attenuated vaccines < 4 weeks prior to Cycle 1 Day
- •Recent infection requiring intravenous antibiotics completed ≤ 7 days before the first dose of study drug, or any uncontrolled active systemic infection.
- •Known bleeding disorders (e.g. von Willebrand's disease) or hemophilia.
- •History of stroke, intracranial hemorrhage, or recent major bleed within 6 months prior to study entry.
- •Participants who require warfarin or other vitamin K antagonists for anticoagulation (other anticoagulants are allowed with approval from the overall principal investigator).
- •Participants who are known at the time of study entry to require concomitant treatment with any medications or substances that are moderate or strong CYP3A inhibitors or inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
- •Known history of human immunodeficiency virus (HIV), active hepatitis C virus (HCV), or hepatitis B virus (HBV).
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to zanubrutinib or venetoclax.
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because zanubrutinib and venetoclax are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanubrutinib or venetoclax, breastfeeding should be discontinued if the mother is treated with zanubrutinib or venetoclax.
- •Participants with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- •Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to study entry.
- •Any life-threatening illness, medical condition, or organ system dysfunction that, in the treating investigator's opinion, could compromise the participant's safety or the integrity of the trial.
- •Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia.
研究组 & 干预措施
Cohort A: BTKi and BCL2i naive
Participants who have never received a BTK inhibitor or a BCL-2 inhibitor
干预措施: Venetoclax (Drug)
Cohort A: BTKi and BCL2i naive
Participants who have never received a BTK inhibitor or a BCL-2 inhibitor
干预措施: Zanubrutinib (Drug)
Cohort B: BTKi or BCL2i exposed without disease progression
Participants who have received prior treatment with a BTK or BCL-2 inhibitor and discontinued treatment for any reason other than disease progression
干预措施: Venetoclax (Drug)
Cohort B: BTKi or BCL2i exposed without disease progression
Participants who have received prior treatment with a BTK or BCL-2 inhibitor and discontinued treatment for any reason other than disease progression
干预措施: Zanubrutinib (Drug)
Cohort C: BTKi exposed and with disease progression
Participants who experienced disease progression on a prior BTK inhibitor. Participants with BTK C481X mutation at enrollment will be excluded.
干预措施: Venetoclax (Drug)
Cohort C: BTKi exposed and with disease progression
Participants who experienced disease progression on a prior BTK inhibitor. Participants with BTK C481X mutation at enrollment will be excluded.
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Rate of undetectable minimal residual disease (uMRD)
时间窗: At the end of cycle 15 (each cycle is 28 days)
Assessed by flow cytometry (FC)
次要结局
- Percentage of uMRD in peripheral blood(After cycle 15At the end of cycle 15 (each cycle is 28 days))
- Progression-free survival (PFS)(1 and 3 years after treatment initiation)
- Overall survival (OS)(1 and 3 years after treatment initiation)
- Complete Response (CR) Rate(At the end of cycle 15 (each cycle is 28 days))
- Overall response Rate (ORR)(At the end of cycle 15 (each cycle is 28 days))
- Percentage of undetectable minimal residual disease (uMRD) in bone marrow with CR(At the end of cycle 15 (each cycle is 28 days))
研究者
Inhye Ahn
Principal Investigator
Dana-Farber Cancer Institute