R-CMOP in Patients With Primary Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of R-CMOP regimen based on mitoxantrone hydrochloride liposome injection in the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL) based on cardiac function screening

Detailed Description
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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. Based on the cardiac safety and efficacy of mitoxantrone liposome, the R-CMOP scheme based on Mitoxantrone liposome for the treatment of initial DLBCL based on cardiac function screening has sufficient theoretical basis and is worth exploring.

Official Title
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An Open, Single-arm, Multicenter Study of R-CMOP Protocol for Primary Treatment of Diffuse Large B-cell Lymphoma Based on Cardiac Function Screening

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Mitoxantrone hydrochloride liposome
* Drug: Cyclophosphamide
* Drug: Vincristine/Vindesine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To participate in the study voluntarily and sign the informed consent (ICF); 18 years ≤ age ≤80 years; Expected survival time ≥3 months; Initial DLBCL confirmed by histopathology; 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 ≥80 g/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); Cardiac function: 50% ≤ LVEF ≤ 55%, or LVEF>55% patients with cardiovascular disease (including left ventricular enlargement (left ventricular diameter: male>60mm; female>55mm), controllable arrhythmia (first degree atrioventricular block, second degree type I atrioventricular block, atrial fibrillation, atrial flutter, ventricular premature beats (<4000 times/24h, mainly single)), myocarditis, pericarditis, structural heart disease, etc.). Exclusion Criteria: Hypersensitivity to any study drug or its components; Uncontrollable systemic diseases (such as progressive infection, uncontrollable 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; 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 treatment. Hepatitis B and hepatitis C active infection (hepatitis B virus surface antigen positive and hepatitis B virus DNA more than 1x10^4 copies /mL; HCV RNA over 1x10^4 copies /mL); Human immunodeficiency virus (HIV) infection (HIV antibody positive); Past or present co-existing malignancies (other than 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); Had primary or secondary central nervous system (CNS) lymphoma or had a history of CNS lymphoma at the time of recruitment Pregnant and lactating women and patients of childbearing age who do not want to take contraceptive measures; Other researchers judged that it was not suitable to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-CMOP<br>R-CMOP：Rituximab, Cyclophosphamide, Mitoxantrone hydrochloride liposomes, Vincristine or Vindesine, Prednisone | Drug: Rituximab<br>* 375 mg/m2, d0<br>Drug: Mitoxantrone hydrochloride liposome<br>* 18 mg/m2, d1<br>Drug: Cyclophosphamide<br>* 750 mg/m2, d1<br>Drug: Vincristine/Vindesine<br>* Vincristine: 1.4 mg/m2, d1(The maximum dose was 2 mg) Vindesine: 3 mg/m2, d1<br>Drug: Prednisone<br>* 60 mg/m2, d1 d5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Objective response rate (ORR) after 6 cycles of R-CMOP chemotherapy | up to 6 cycles of chemotherapy (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate(CRR) | Complete remission rate(CRR) after 6 cycles of R-CMOP chemotherapy | up to 6 cycles of chemotherapy (each cycle is 21 days) | 
| Duration of remission(DOR) | Time from reaching CR or PR for the first time to disease progression | up to 6 cycles of chemotherapy (each cycle is 21 days) | 
| Progression-Free-Survival rate | from date of inclusion to date of progression, relapse, or death from any cause | 1 year | 
| Overall survival rate | from the date of inclusion to date of death, irrespective of cause | 1 year | 
| Adverse events (AE) | The safety of the drug was evaluated by NCI-CTC AE 5.0 standard | From the first day of medication to 28 days after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, R-CMOP, Mitoxantrone liposome