Efficacy and Safety of Zanubrutinib Combined With G-CVP Regimen in Previously Untreated Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- CRR
研究概览
简要总结
The goal of this clinical trial is to learn the efficacy and safety of zanubrutinib in combination with G-CVP in previously untreated follicular lymphoma patients The main questions it aims to answer are: (1) Efficacy and safety of patients receiving zanubrutinib, obinutuzumab combined with cyclophosphamide, vincristine, and prednisone (CVP) regimen. (2) The difference in efficacy of patients with different minimal residual disease (MRD) status after treatment.
Participants will receive zanubrutinib combined with G-CVP, maintenance therapy will be determined by the MRD status after treatment.
详细描述
Follicular lymphoma (FL), accounting for nearly 20% of non - Hodgkin lymphomas, is an indolent B - cell neoplasm originating from follicular center B cells. Over 90% of patients are at stage Ⅲ/Ⅳ at onset. For stage Ⅲ/Ⅳ patients requiring treatment, CD20 monoclonal antibody - chemotherapy combinations are the most commonly used treatment both domestically and internationally. Though FL has a high response rate to traditional immunochemotherapy, it remains incurable by such means. Also, cytotoxic therapy's side effects are a key concern. There's an urgent need in clinical practice to enhance therapeutic efficacy while reducing side effects.
Obinutuzumab, a type II anti - CD20 monoclonal antibody, stands out from type I by boosting antitumor activity through enhanced direct cytotoxicity (DCD) and antibody - dependent cellular cytotoxicity (ADCC), and cutting complement - dependent cytotoxicity (CDC) - related resistance. Studies comparing obinutuzumab - chemotherapy with rituximab - chemotherapy in untreated FL have confirmed that the former brings sustained progression - free survival (PFS) benefits. Compared to CHOP or bendamustine combinations, it has a lower incidence of grade 3 - 5 adverse events when used with CVP, showing better tolerability. Zanubrutinib, a novel, highly - selective small - molecule BTK inhibitor developed in China, offers superior efficacy and safety due to its high kinase selectivity. Its combination with obinutuzumab has achieved remarkable results in relapsed/refractory FL patients.
In this study, we will treat untreated FL patients with zanubrutinib, obinutuzumab, and CVP chemotherapy. We expect this multi - mechanism drug combination to improve efficacy. Also, by replacing CHOP's anthracycline component, the regimen may provide better safety, thus offering a more effective and safer individualized treatment for untreated FL patients.
Untreated FL patients in the study will receive zanubrutinib, obinutuzumab, and CVP chemotherapy. Then, based on their MRD status, they'll undergo maintenance with either obinutuzumab alone or the combination. The primary endpoint is the complete remission (CR) rate; secondary endpoints include overall response rate (ORR), PFS, overall survival (OS), and adverse event (AE) rates.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following criteria to be eligible:
- •Histologically confirmed CD20-positive FL (grades 1, 2, or 3a), diagnosed according to the WHO 2022 criteria; 2, Clear indication for treatment: symptoms affecting normal work and life; end-organ dysfunction; cytopenia due to bone marrow involvement by lymphoma; bulky disease (per GELF criteria); persistent or rapidly progressive disease;
- •No prior systemic therapy for lymphoma;
- •Age 18-80 years;
- •Eastern cooperative oncology group (ECOG) performance status (PS) < 2;
- •Expected survival > 2 years;
- •At least one measurable lesion with a longest diameter ≥ 1.5 cm or extranodal lesion ≥ 1 cm;
- •Willingness to participate in the study and comply with treatment and follow-up.
排除标准
- •Patients will be excluded if they meet any of the following criteria:
- •Pregnant or breastfeeding women;
- •Abnormal liver or kidney function, defined as: serum direct/indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), or serum creatinine > 2 × upper limit of normal (ULN); creatinine clearance < 60 mL/min (unless due to lymphoma involvement);
- •History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
- •Absolute neutrophil count (ANC) < 1.5 × 10⁹/L, platelets < 75 × 10⁹/L, or hemoglobin < 70 g/L (unless due to bone marrow involvement by lymphoma);
- •Long-term use of strong or moderate CYP3A inducers;
- •Known hypersensitivity to any component of the study drug;
- •Other active malignancies, except: cured non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, or other malignancies with disease-free survival > 5 years;
- •Severe concurrent infections;
- •Drug abuse, medical, psychological, or social conditions that may interfere with study participation or result evaluation;
- •Investigator-deemed ineligibility for the study.
研究组 & 干预措施
ZG- CVP
Zanubrutinib , obinutuzumab , cyclophosphamide , vincristine, and prednisone tablets were used every 21 days as a treatment cycle. Six cycles of treatment were completed, and the efficacy was reviewed every two cycles. Patients with progressive disease (PD) were excluded from the group. MRD was detected after six cycles. If MRD was negative, routine maintenance therapy was performed . If MRD was positive, Zanubrutinib was added to the conventional maintenance therapy for 12 months.
干预措施: zanubrutinib, obinutuzumab,combined with CVP (Drug)
结局指标
主要结局
CRR
时间窗: From date of enrollment until the date of first documented CR assessed up to 2.5 years.
CRR (%) is defined as the number of patients achieving a complete response as a proportion of total patients evaluable for response.
次要结局
- ORR(From date of enrollment until the date of first documented response assessed up to 2.5 years.)
- PFS(From date of enrollment until the date of first documented progression assessed up to 5 years.)
- OS(From date of enrollment until the date of first documented death assessed up to 5 years.)
研究者
Zhitao Ying
chief physician
Cancer Institute and Hospital, Chinese Academy of Medical Sciences