An Open, Single-arm, Multi-center Clinical Trial of Molecular Subtype-guided R-MINE+X Regimen in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- Objective Response Rate(ORR)
研究概览
简要总结
Based on the modified R-MINE of mitoxantrone hydrochloride liposome, the corresponding targeted drug (X) was added according to the genotyping detected by second-generation gene sequencing (NGS) to explore the effectiveness and safety of R-MINE+X in the treatment of recurrent/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
详细描述
Compared with traditional mitoxantrone, mitoxantrone liposomes can significantly prolong the survival time of patients and reduce the cardiotoxicity and non-hematological toxicity of anthracycline drugs. At present, there are no studies on the efficacy and safety of R-MINE+X regimen based on molecular typing in the treatment of R/R DLBCL. Therefore, based on NGS, R/R DLBCL was divided into different molecular types (MCD subtype, BN2 subtype, EZB subtype, A53 subtype and other subtype), and on this basis, different molecular types of targeted drugs (X: MCD/BN2 subtype - BTK inhibitor, EZB subtype - Chidamide, A53 subtype - PD-1 monoclonal antibody and other type - lenalidomide) were used to treat R/R DLBCL. The main purpose was to observe the effectiveness and safety of the program in R/R DLBCL.
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
- •Join the study voluntarily and sign the informed consent;
- •Age ≤ 18 years old ≤75 years old;
- •Expected survival time ≥3 months;
- •Recurrent or refractory diffuse large B-cell lymphoma confirmed by histopathology;
- •Consistent with relapsed or refractory lymphoma: Relapsed lymphoma refers to lymphoma that relapsed after CR obtained from initial chemotherapy. Refractory lymphoma is diagnosed by meeting any of the following criteria: 1) tumor shrinkage < 50% or progression after 4 courses of chemotherapy prescribed by the standard regimen; 2) CR was achieved by standard chemotherapy, but recurrent within half a year; 3) Relapse for two or more times after CR; 4) Recurrence after hematopoietic stem cell transplantation;
- •There must be at least one evaluable or measurable lesion in line with Lugano2014 criteria: lymph node lesion, the length and diameter of detectable lymph node must be greater than 1.5cm; For non-lymph node lesions, the diameter of extrinsic lesions should be > 1.0cm;
- •ECOG score 0-2;
- •Bone marrow function: neutrophil count ≥1.5×10^9/L, platelet count ≥75×10^9/L, hemoglobin ≥80g/L (neutrophil count ≥1.0×10^9/L, platelet count ≥50×10^9/L, hemoglobin ≥75g/L in patients with bone marrow involvement);
- •Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times the upper limit of normal value (≤5 times the upper limit of normal value for patients with liver invasion); Total bilirubin ≤1.5 times the upper limit of normal value (≤3 times the upper limit of normal value for patients with liver invasion);
排除标准
- •The subject's previous history of antitumor therapy meets one of the following conditions:
- •Previous recipients of mitoxantrone or mitoxantrone liposomes;
- •Prior treatment with doxorubicin or anthracycline with a cumulative dose of doxorubicin > 360 mg/m2 (1 mg of doxorubicin for other anthracyclines);
- •Patients who had received autologous hematopoietic stem cell transplantation or had received allogeneic hematopoietic stem cell transplantation within 100 days of the first medication;
- •Received anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, taking anti-tumor active Chinese medicine, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the drug in this study;
- •Hypersensitivity to any investigational drug or its components;
- •Uncontrolled systemic diseases (such as advanced infections, uncontrolled hypertension, diabetes, etc.);
- •Cardiac function and disease conform to one of the following conditions:
- •Long QTc syndrome or QTc interval >480 ms;
- •Complete left bundle branch block, complete right bundle branch block with left anterior branch block, second degree type II, or third degree atrioventricular block;
- •severe, uncontrolled arrhythmias requiring medical treatment;
- •New York College of Cardiology Grade ≥ III;
- •A history of acute myocardial infarction, unstable angina pectoris, severely unstable ventricular arrhythmias or any other arrhythmia requiring treatment, a history of clinically severe pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction abnormalities within the 6 months prior to recruitment.
- •Hepatitis B and hepatitis C active infection (hepatitis B virus surface antigen positive and hepatitis B virus DNA more than 1x10^3 copies /mL; HCV RNA over 1x10^3 copies /mL);
- •Human immunodeficiency virus (HIV) infection (HIV antibody positive);
- •Past or present co-existing malignancies (in addition to non-melanoma basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix, and other malignancies that have been effectively controlled without treatment in the past five years);
- •Primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma at the time of recruitment;
- •There is significant gastrointestinal disease at the time of screening that may affect drug intake, transport or absorption (e.g. inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
- •Pregnant and lactating women and patients of childbearing age who do not wish to take contraceptive measures;
- •Situations in which other researchers have determined that participation in this study is not appropriate.
研究组 & 干预措施
R-MINE+X
R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide
X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide
干预措施: Rituximab (Drug)
R-MINE+X
R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide
X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide
干预措施: Mitoxantrone hydrochloride liposome (Drug)
R-MINE+X
R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide
X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide
干预措施: Isophosphamide (Drug)
R-MINE+X
R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide
X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide
干预措施: Etoposide (Drug)
结局指标
主要结局
Objective Response Rate(ORR)
时间窗: up to 4 cycles of chemotherapy(each cycle is 21 days)
Objective response rate (ORR) after 4 cycles of R-MINE+X chemotherapy
次要结局
- Adverse events (AE)(From the first day of medication to 28 days after the last dose)
- Complete remission rate(CRR)(up to 4 cycles of chemotherapy(each cycle is 21 days))
- Duration of remission(DOR)(up to 4 cycles of chemotherapy(each cycle is 21 days))
- Overall survival rate(1 year)
- Progression-Free-Survival rate(1 year)