A Single Arm, Open-label Study of MRD-Guided Zanubrutinib in Combination With Sonrotoclax in Adult Patients With Treatment Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 66
- 主要终点
- 4-Year Progressive Free Survival (PFS) Rate
研究概览
简要总结
This is a single-arm, open-label study of sonrotoclax plus zanubrutinib with MRD-driven treatment duration in patients with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
The primary goal of this study is to evaluate the efficacy of MRD-guided zanubrutinib plus sonrotoclax for first-line CLL/SLL treatment.
详细描述
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are often considered different variations of the same disease due to their many similarities. There is an urgent need for new treatments to improve patients' quality of life, prolong survival, and manage disease-related symptoms.
There are several different methods for treating front-line therapy, including Chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitors (BTKis), and BCL-2 inhibitors (BCL2is). Continuous treatment with BTK inhibitors is necessary for the treatment of CLL or SLL. However, younger patients may need to limit their therapeutic duration. The combination of BTK inhibitors and BCL-2 inhibitors is believed to be an optimizing regimen that provides a limited duration of therapy.
The main aim of this study is to assess whether MRD-guided zanubrutinib, in combination with sonrotoclax, can be an effective first-line treatment option for adult patients with treatment-naïve CLL or SLL. The goal is to achieve long-lasting and more profound responses, which could allow for the possibility of discontinuing treatment.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment naïve adult patients with diagnosis of CLL/SLL requiring treatment according to iwCLL guidelines 2018
- •Measurable nodal disease by CT/MRI.
- •Adequate hematologic function
- •Adequate hepatic and renal function
- •Eastern Cooperative Oncology Group
- •(ECOG) performance status of 0-2
- •Expected survival period > 6 months
排除标准
- •Any prior systemic therapy used for treatment of CLL/SLL
- •With history of prolymphocytic leukemia, known or currently suspected Richter's transformation
- •Known central nervous system involvement by leukemia or lymphoma
- •Confirmed progressive multifocal leukoencephalopathy (PML)
- •Severe or debilitating pulmonary disease
- •Clinically significant cardiovascular disease
- •Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura requiring treatment
- •History of other malignancies
- •Prior therapy with study drugs within 4 weeks before screening
- •Active fungal, bacterial, and/or viral infection requiring systemic therapy
- •Known allergy to zanubrutinib or sonrotoclax or any pharmaceutical excipients
- •Pregnant or lactating women
- •Vaccinated with live vaccines within 28 days prior to enrollment
- •Serologically positive of human immunodeficiency virus (HIVAb), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •History of stroke or intracranial hemorrhage within 6 months
- •Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
研究组 & 干预措施
Sonrotoclax Plus Zanubrutinib
-
Participants will receive from the start of Cycle 1 a standard dose of zanubrutinib twice daily orally for three cycles and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses twice a week until the target dose is reached from Cycle 5 and continuing until the end of Cycle 15 (each cycle is 28 days). Patients with a measurable minimal residual disease (MRD) will receive another 12 cycles of Zanubrutinib in combination with sonrotoclax until their MRD is undetectable.
-
Interventions:
-
Drug: Sonrotoclax
-
Drug: Zanubrutinib
干预措施: Sonrotoclax (Drug)
Sonrotoclax Plus Zanubrutinib
-
Participants will receive from the start of Cycle 1 a standard dose of zanubrutinib twice daily orally for three cycles and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses twice a week until the target dose is reached from Cycle 5 and continuing until the end of Cycle 15 (each cycle is 28 days). Patients with a measurable minimal residual disease (MRD) will receive another 12 cycles of Zanubrutinib in combination with sonrotoclax until their MRD is undetectable.
-
Interventions:
-
Drug: Sonrotoclax
-
Drug: Zanubrutinib
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
4-Year Progressive Free Survival (PFS) Rate
时间窗: 4 years after enrollment
PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by investigators
次要结局
- Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD)(At screening, the end of Cycle 14 and Cycle 26 (each cycle is 28 days))
- Complete Response Rate (CRR; Complete Response/Complete Response with Incomplete Blood Count Recovery [CR/CRi]) Rate(Up to 4 years)
- Overall Response Rate (ORR)(Up to 4 years)
- Duration of Response (DOR)(Up to 4 years)
- Progression Free Survival (PFS)(Up to 4 years)
- Overall Survival (OS)(Up to 4 years)
- Time to Next Therapy (TTNT)(Up to 4 years)
- Overall survival rate(Up to 4 years)
研究者
Qiu Lugui
Institute of Hematology & Blood Diseases Hospital, China
Institute of Hematology & Blood Diseases Hospital, China