Zanubrutinib Combined With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With p53 Protein Expression
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Complete response rate (CRR)
研究概览
简要总结
This study aim to evaluate the efficacy and safety of zanubrutinib combined with R-CHOP in the treatment of DLBCL patients with p53 protein expression.
详细描述
This is a prospective, single arm, single center study,it plans to recruit 41 newly diagnosed DLBCL patients with p53 protein expression(≥50%).According to Simon's two-stage optimal design criteria, 19 eligible patients were recruited in the first phase, and at least 12 patients were required to achieve complete response to enter the second phase. In phase 2, additional 22 patients were recruited. These patients will receive zanubrutinib plus RCHOP for 6 cycles. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive or stable disease will be discontinued from treatment，Participants with complete/partial response will continue ZRCHOP until 6 cycles are completed.After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years, ≤ 75 years, both sexes;
- •Diff use large B-cell lymphoma diagnosed by histopathology without previous systemic DLBCL treatment;
- •ECOG score: 0-2;
- •Predicted survival ≥3 months;
- •Patients with positive p53 expression detected by immunohistochemistry (≥50% );
- •The patients had certain conditions of organ function reserve, and the laboratory tests within 1 week before enrollment met the following conditions:
- •Blood routine: neutrophil count (NEUT) ≥1.5×10^9/L, platelet count (PLT)
- •≥75×10^9/L, hemoglobin (HGB) ≥80 g/L; G-CSF was not used in the past 7 days (the researchers judged that the lymphoma-induced cytopenia could be included).
- •Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of the normal range (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; If liver metastases were present, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤2.0×ULN or creatinine clearance (CCr) ≥60ml/min;
- •Cardiac function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular conduction block above grade I;
- •Thyroid function: thyroid stimulating hormone (TSH) was within the normal range. If TSH is abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal range or abnormal without clinical significance.
- •According to the Lugano2014 assessment criteria, patients must have measurable lesions, defined as the longest diameter of at least one nodule > 1.5cm, or the longest diameter of at least one nodule > 1cm, and at least two vertical diameters that can be accurately measured.
- •Patients volunteered to participate in the trial, understood the study procedure, and were able to sign in-person informed consent.
排除标准
- •Patients with definite lymphoma central nervous system (CNS) infiltration, including brain parenchyma, meningeal invasion, or spinal cord compression;
- •severe or uncontrolled infection;
- •with active autoimmune disease;
- •Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc. (the decision was left to the investigator);
- •patients who received the live attenuated vaccine within 4 weeks before the first dose or planned to receive the live attenuated vaccine during the study;
- •The subject has previous or co -e xis ting other malignant tumors; Patients with basal cell carcinoma of the skin and uterine and neck carcinoma in situ who had been cured for more than 3 years, and patients with other malignant tumors who had been cured for more than 5 years were considered for inclusion.
- •HIV-positive patients with active hepatitis B ( HBV-DNA > 100 copies/m L), positive HCV antibody, or abnormal HCV-RNA
- •Women who were pregnant or lactating, women who planned to become pregnant between the study period and 6 months after the last dose, or men whose partners planned to become pregnant, who were unwilling to use a medically approve defective contraceptive method (e.g., intrauterine device or condom ) during the trial;
- •were allergic to any of the drugs in the study protocol;
- •ineligible for inclusion as judged by the investigator ;
研究组 & 干预措施
Z-RCHOP
Patients with newly diagnosed DLBCL with p53 expression were treated with a combination of Zanubrutinib and RCHOP.
干预措施: Zanubrutinib plus RCHOP (Drug)
结局指标
主要结局
Complete response rate (CRR)
时间窗: At the end of cycle 6 (each cycle is 21 days )
To evaluate the efficacy of anti-lymphoma
次要结局
- Progression-free survival (PFS)(From date of initiation therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- Overall response rate (ORR)(At the end of cycle 6 (each cycle is 21 days ))
- Overall survival (OS)(From date of initiation therapy until the date of death from any cause, assessed up to 60 months)
- Rate of AE and SAE(from the initiation of the first dose to 28 days after the last dose)
研究者
Liling Zhang
Professor
Huazhong University of Science and Technology