Zanubrutinib and Rituximab Followed by R-DHAOx (Rituximab, Dexamethasone, Cytarabine and Oxaliplatin) Regimen Then Maintenance with Zanubrutinib for Newly-Diagnosed Mantle Cell Lymphoma (MCL): a Single Arm, Open Label, Multi-center Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Complete remission rate after PART A
研究概览
简要总结
This phase 2 trial studies the efficacy and safety of zanubrutinib plus rituximab followed by R-DHAOx (rituximab, dexamethasone, cytarabine and oxaliplatin) regimen then maintenance with zanubrutinib for newly-diagnosed Mantle Cell Lymphoma (MCL).
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
- •Histologically confirmed CD20 positive mantle cell lymphoma;
- •Patients with MCL-related symptomatic and need immediate therapy; Include any of the following: (1) Blastoid variant (2) Pleomorphic variant (3) Ki-67 ≥30% (4) Bulky mass > 7 cm or ≥2 tumors, each ≥5 cm in diameter (5) Mutations in TP53, c-MYC or NOTCH genes (6) Size of spleen ≥20 cm (7) Lymphoma B symptoms (8) Mantle Cell International Prognostic Score (MIPI) > 3 (9) Lymphoma threatening organ function (10) Elevated lactate dehydrogenase (11) Peripheral blood white blood cell > 50×10^9/L (12) Pancytopenia due to bone marrow involvement (13) Pain due to lymphoma;
- •Patients received no prior anti-lymphoma treatment;
- •At least one evaluable lesion according to 2014 Lugano criteria;
- •Ann Arbor stage II-IV;
- •Eastern Cooperative Oncology Group (ECOG) of 0-2;
- •Life expectancy > 3 months;
- •Able to participate in all required study procedures;
- •Proper functioning of the major organs: 1) The absolute value of neutrophils (>1.5×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 80 g/L); 4) Serum creatinine <1.5 times Upper Limit Normal (ULN) ; 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) < 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range at screening time);
排除标准
- •Involvement of central nervous system (CNS)
- •Patients with Hemophagocytic syndrome;
- •Patients with active bleeding, bleeding tendency or require anticoagulation treatment;
- •Patients require treatment with strong CYP3A inhibitors;
- •Uncontrolled active infection, with the exception of tumor-related B symptom fever;
- •History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;
- •Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;
- •Diagnosed with or receiving treatment for malignancy other than lymphoma;
- •Pregnant or breastfeeding women;
- •Other researchers consider it unsuitable for patients to participate in this study.
研究组 & 干预措施
zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance
Part A (Zanubrutinib and Rituximab): Patients receive zanubrutinib on days 1-28 and rituximab on day 1. Treatment cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve CR.
PART B (Consolidation chemotherapy of R-DHAOx): Patients receive R-DHAOx regimen every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Elderly patients (> 65 years old) and patients who achieved CR and minimal residual disease negative after PART B receive zanubrutinb maintenance therapy. Young patients (<65 years old) who achieved CR but minimal residual disease positive after PART B can receive autologous stem cell transplantation and then zanubrutinb maintenance therapy. Patients with PD, SD or PR after PART B quit the trial.
ZANUBRUTINB MAINTENANCE: Patients receive zanubrutinib every day for up to one year.
干预措施: Zanubrutinib and Rituximab (Drug)
zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance
Part A (Zanubrutinib and Rituximab): Patients receive zanubrutinib on days 1-28 and rituximab on day 1. Treatment cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve CR.
PART B (Consolidation chemotherapy of R-DHAOx): Patients receive R-DHAOx regimen every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Elderly patients (> 65 years old) and patients who achieved CR and minimal residual disease negative after PART B receive zanubrutinb maintenance therapy. Young patients (<65 years old) who achieved CR but minimal residual disease positive after PART B can receive autologous stem cell transplantation and then zanubrutinb maintenance therapy. Patients with PD, SD or PR after PART B quit the trial.
ZANUBRUTINB MAINTENANCE: Patients receive zanubrutinib every day for up to one year.
干预措施: R-DHAOx (Drug)
zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance
Part A (Zanubrutinib and Rituximab): Patients receive zanubrutinib on days 1-28 and rituximab on day 1. Treatment cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve CR.
PART B (Consolidation chemotherapy of R-DHAOx): Patients receive R-DHAOx regimen every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Elderly patients (> 65 years old) and patients who achieved CR and minimal residual disease negative after PART B receive zanubrutinb maintenance therapy. Young patients (<65 years old) who achieved CR but minimal residual disease positive after PART B can receive autologous stem cell transplantation and then zanubrutinb maintenance therapy. Patients with PD, SD or PR after PART B quit the trial.
ZANUBRUTINB MAINTENANCE: Patients receive zanubrutinib every day for up to one year.
干预措施: Zanubrutinib Maintenance (Drug)
结局指标
主要结局
Complete remission rate after PART A
时间窗: 3 years
Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.
次要结局
- Complete remission rate after study treatment(3 years)
- Overall Survival(5 years)
- Objective Response rate(3 years)
- Time to Response(3 years)
- Progression Free Survival(5 years)
- Percentage of Participants With Adverse Events(3 years)
- Duration of Response(5 years)
研究者
Qingqing Cai
Chief physician
Sun Yat-sen University