r-mine+x in patients with relapsed/refractory diffuse large b-cell lymphoma

Conditions: Diffuse Large B-cell Lymphoma

Summary: 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).

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.

Eligibility criteria:
inclusion criteria: 1. join the study voluntarily and sign the informed consent; 2. age ≤ 18 years old ≤75 years old; 3. expected survival time ≥3 months; 4. recurrent or refractory diffuse large b-cell lymphoma confirmed by histopathology; 5. 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; 6. 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; 7. ecog score 0-2; 8. 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); 9. 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); exclusion criteria: 1. the subject's previous history of antitumor therapy meets one of the following conditions: 1. previous recipients of mitoxantrone or mitoxantrone liposomes; 2. prior treatment with doxorubicin or anthracycline with a cumulative dose of doxorubicin \> 360 mg/m2 (1 mg of doxorubicin for other anthracyclines); 3. patients who had received autologous hematopoietic stem cell transplantation or had received allogeneic hematopoietic stem cell transplantation within 100 days of the first medication; 4. 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; 2. hypersensitivity to any investigational drug or its components; 3. uncontrolled systemic diseases (such as advanced infections, uncontrolled hypertension, diabetes, etc.); 4. cardiac function and disease conform to one of the following conditions: 1. long qtc syndrome or qtc interval \>480 ms; 2. complete left bundle branch block, complete right bundle branch block with left anterior branch block, second degree type ii, or third degree atrioventricular block; 3. severe, uncontrolled arrhythmias requiring medical treatment; 4. new york college of cardiology grade ≥ iii; 5. 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. 5. 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); 6. human immunodeficiency virus (hiv) infection (hiv antibody positive); 7. 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); 8. primary or secondary central nervous system (cns) lymphoma or history of cns lymphoma at the time of recruitment; 9. 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.); 10. pregnant and lactating women and patients of childbearing age who do not wish to take contraceptive measures; 11. situations in which other researchers have determined that participation in this study is not appropriate.

Keywords: dlbcl r-mine+x mitoxantrone liposome