mitoxantrone hydrochloride liposome combined with rituximab and lenalidomide (m+r2) in patients with relapsed and refractory diffuse large b-cell lymphoma

Conditions: Diffuse Large B-cell Lymphoma

Summary: to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with rituximab and lenalidomide in the treatment of relapsed and refractory diffuse large b-cell lymphoma (dlbcl).

this is a prospective, single-arm, multicenter phase ⅱ clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with rituximab and lenalidomide in patients with relapsed and refractory diffuse large b-cell lymphoma (dlbcl). mitoxantrone hydrochloride liposome will be given on day 1 at the dose of 20 mg/m2 and be combined with rituximab and lenalidomide. a maximum of 6 cycles of therapy are planned.

Eligibility criteria:
inclusion criteria: * 1.subjects fully understand and voluntarily participate in this study and sign the informed consent form (icf); * 2.60-75 years old; * 3.expected survival ≥ 3 months; * 4.subjects with histologically confirmed diagnosis of relapsed and refractory diffuse large b-cell lymphoma who have received at least 4 cycles of first-line chemotherapy including rituximab and anthracyclines; relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (cr) after initial chemotherapy; refractory lymphoma subjects meet one of the following conditions: 1) the tumor shrinks \<50% or disease progression after 4 cycles of standard chemotherapy,; 2) cr after standard chemotherapy, but relapse within half a year; 3) 2 or more relapses after cr; 4) relapse after hematopoietic stem cell transplantation; * 5.subjects who are not eligible for transplantation or do not plan to undergo transplantation at the beginning of the study; * 6.ecog performance status: 0-2; * 7.subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length should be \> 1.5cm; for non-lymph node lesions, the length should be \> 1.0cm; * 8.bone marrow function: absolute neutrophil count ≥1.5×109/l, platelet count ≥75×109/l, hemoglobin ≥ 80g/l (absolute neutrophil can be relaxed to ≥ 1.0×109/l, platelet count can be relaxed to ≥50×109/l, hemoglobin can be relaxed to ≥75 g/l in subjects with poor bone-marrow reserve); * 9.liver and kidney function: serum creatinine ≤ 1.5×uln (upper limit of normal); ast and alt ≤ 2.5×uln (≤ 5×uln for subjects with liver metastases); total bilirubin ≤ 1.5×uln (≤ 3×uln for subjects with liver metastases). exclusion criteria: * 1. the subject had previously received any of the following anti-tumor treatments: 1. subjects who have been treated with mitoxantrone or mitoxantrone liposomes; 2. previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin); 3. subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs within 4 weeks or 5 t1/2s before the first administration of the study drugs; 4. subjects who received lenalidomide. * 2.subjects with refractory lymphoma meet one of the following criteria: 1) tumors assessed as sd/pd after ≥2 lines of chemotherapy; 2) subjects relapse within 6 months after transplantation. * 3.hypersensitivity to any study drug or its components; * 4.uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.) * 5.heart function and disease meet one of the following conditions: 1. long qtc syndrome or qtc interval \> 480 ms; 2. complete left bundle branch block, grade ii or iii atrioventricular block; 3. serious and uncontrolled arrhythmias requiring drug treatment; 4. new york heart association grade ≥ iii; 5. cardiac ejection fraction (lvef)\< 50%; 6. a history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ecg evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment. * 6.hepatitis b and hepatitis c active infection (plus hbv dna if one positive for hepatitis b surface antigen or core antibody and hbv dna more than 1×103 copy/ml excluded; plus hcv rna if hepatitis c antibody positive and hcv rna more than 1×103 copy/ml exclude) * 7.baseline b-type pro-brain natriuretic peptide (nt-probnp) \> 1800pg/ml, troponin i (ctni) \> uln of our center, and the retest data is still higher than the above range after three days; * 8.human immunodeficiency virus (hiv) infection (hiv antibody positive); * 9.subjects with other malignant tumors past or present (except for non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in control, and other malignant tumors that have been effectively controlled without treatment within the past five years); * 10.subjects suffering from primary or secondary central nervous system (cns) lymphoma or a history of cns lymphoma at the time of recruitment; * 11.unsuitable subjects for this study determined by the investigator.