Safety and Efficacy of Zanubrutinib in Combination With Rituximab and Venetoclax in Previously Untreated Follicular Lymphoma: An Open Label, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- CR rate
研究概览
简要总结
This is a single center, open label, single arm phase II clinical trial. The objective of this study is to assess the feasibility and efficacy of zanubrutinib combined with venetoclax and Rituximab in patients with previously untreated follicular lymphoma (FL) .
详细描述
Follicular lymphoma (FL)is the most common inert non Hodgkin's lymphoma (iNHL). Their natural courses are slow but highly variable. The standard first-line treatment of advanced FL is based on rituximab. Whether combined with chemotherapy or not, it can induce lasting remission, but it is usually incurable. Although the first-line immunochemotherapy regimen has high efficacy, it also has high toxicity. Cytotoxic chemotherapy is related to many side effects, including bone marrow suppression and immunosuppression, gastrointestinal and cardiac toxicity, neurotoxicity and the occurrence of secondary tumors. About 20% of FL patients relapse within 2 years after first-line chemotherapy. The overall prognosis of these patients is poor. This clinical trial aims to evaluate the feasibility and efficacy of free-chemotherapy regimen (zanubrutinib combined with venetoclax and Rituximab) in patients with previously untreated follicular lymphoma.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated.
- •Stage II, III, or IV disease.
- •Able and willing to provide written informed consent and to comply with the study protocol.
- •at least one measurable disease.
- •Must be in need of therapy as evidenced by at least one of the following criteria:
- •Presence of at least one B symptom: Fever (> 38 Celsius [C]) not due to infectious etiology, or Night sweats, or Weight loss > 10% in the past 6 months;
- •Fatigue due to lymphoma;
- •Splenomegaly (> 13 cm);
- •Compression syndrome (ureteral, orbital, gastrointestinal);
- •Any of the following cytopenias, due to lymphoma: Hemoglobin ≤ 10 g/dL, or Platelets ≤ 100 x 10^9/L, or Absolute neutrophil count (ANC) < 1.5 x 10^9/L;
- •Pleural or peritoneal effusion;
- •Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta (B)2 microglobulin > ULN;
- •Other lymphoma-mediated symptoms as determined by the treating physician.
- •ANC > 1.0 x 10^9/L (for patients without bone marrow involvement by lymphoma)
- •Platelet count > 50 x 10^9/L (for patients without bone marrow involvement by lymphoma)
- •Prothrombin time (PT)/international normal ratio (INR) < 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR ≤ 3.0)
- •Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x ULN
- •Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
- •Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
- •Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
排除标准
- •Known active central nervous system lymphoma or leptomeningeal disease
- •Follicular lymphoma with evidence of diffuse large B-cell transformation
- •Grade 3b follicular lymphoma
- •Any prior history of other malignancy besides follicular lymphoma
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •Patients who have undergone major surgery within 14 days
- •The researchers believe that it is not advisable for the participant to take part in this trial.
研究组 & 干预措施
Treatment (zanubrutinib, venetoclax, rituximab)
stage I (cycles 1-3, every 4 weeks): zanubrutinib PO 160mg, BID; rituximab IV on day 1.
stage II (cycles 4-9, every 4 weeks): if complete response : zanubrutinib PO 160mg, BID; rituximab IV on day 1.
if no complete response : zanubrutinib PO160mg, BID; rituximab IV on day 1 and Venetoclax PO (100mg D1, 200mg D2, and 400mg D3 of cycle 4; 400mg QD).
干预措施: Rituximab (Biological)
Treatment (zanubrutinib, venetoclax, rituximab)
stage I (cycles 1-3, every 4 weeks): zanubrutinib PO 160mg, BID; rituximab IV on day 1.
stage II (cycles 4-9, every 4 weeks): if complete response : zanubrutinib PO 160mg, BID; rituximab IV on day 1.
if no complete response : zanubrutinib PO160mg, BID; rituximab IV on day 1 and Venetoclax PO (100mg D1, 200mg D2, and 400mg D3 of cycle 4; 400mg QD).
干预措施: Zanubrutinib (Drug)
Treatment (zanubrutinib, venetoclax, rituximab)
stage I (cycles 1-3, every 4 weeks): zanubrutinib PO 160mg, BID; rituximab IV on day 1.
stage II (cycles 4-9, every 4 weeks): if complete response : zanubrutinib PO 160mg, BID; rituximab IV on day 1.
if no complete response : zanubrutinib PO160mg, BID; rituximab IV on day 1 and Venetoclax PO (100mg D1, 200mg D2, and 400mg D3 of cycle 4; 400mg QD).
干预措施: Venetoclax (Drug)
结局指标
主要结局
CR rate
时间窗: Within 6 months of therapy completion
Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with a CR will be tabulated.
次要结局
- Overall response rate (ORR)(Within 6 months of therapy completion)
- Progression-free survival(up to two years)
- Overall survival(up to two years)
- Incidence of Treatment-Emergent Adverse Events(Up to 90 days after the last dose of study drugs)
研究者
Han weidong
Chief physician.
Chinese PLA General Hospital