Safety and Efficacy Study of CNOP Chemotherapy in Diffuse Large B Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Mitoxantrone Hydrochloride Liposome Injection plus Cyclophosphamide,Vincristine and Prednison(CNOP)is safe and effective in the treatment of Diffuse Large B Cell Lymphoma.

Detailed Description
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Mitoxantrone Hydrochloride Liposome Injection is a kind of anthraquinone compounds, and its antineoplastic effect has been viewed in preclinical tests. The investigator´s phaseⅠstudy has shown that the drug´s toxicity is manageable and the tolerable does is 20 mg/m2. The purpose of this study is to determine whether Mitoxantrone Hydrochloride Liposome Injection plus Cyclophosphamide,Vincristine and Prednison(CNOP)is safe and effective in the treatment of Diffuse Large B Cell Lymphoma.Patients physical state, symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if Mitoxantrone Hydrochloride Liposome Injection plus Cyclophosphamide,Vincristine and Prednison(CNOP)is safe and effective in the treatment of Diffuse Large B Cell Lymphoma.

Official Title
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Safety and Efficacy Study of Mitoxantrone Hydrochloride Liposome Injection Plus Cyclophosphamide,Vincristine and Prednison (CNOP)in Diffuse Large B Cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to study specific screening procedures; Favorable index of curative effect of Diffuse Large B Cell Lymphoma confirmed by histological analysis; ≥ 18 and ≤ 70 years of age, male or female; Advanced Lymphoma and standard treatments failed; May benefit from anthracycline-based drugs; ECOG performance status of 0-2; More than 4 weeks from the last chemotherapy, more than 4 weeks from the last biotherapy, more than 4 weeks from the last clinical trial drug therapy; Life expectancy of more than 3 months; Sexually active women of childbearing potential must use a medically acceptable form of contraception; Adequate hepatic, renal, cardiac and hematologic functions: leukocyte≥3.5×10^9/L,neutrophils≥2.0×10^9/L,platelets≥100×10^9/L, hemoglobin≥90g/L,creatinine clearance rate≤1.5×ULN, serum bilirubin≤1.5×ULN, ALT≤2.5×ULN(5×for liver metastasis),AST≤2.5×ULN(5×for liver metastasis), alkaline phosphatase≤200 IU/L,Electrocardiogram appeared to be essentially normal, ejection fraction of Heart Doppler ultrasound appeared to be normal. Exclusion Criteria: Pregnant or lactating women; Patients with Multiple sclerosis; Suffering from serious internal disease, including serious heart attack, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension,uncontrolled infection, Active peptic ulcer; Mitoxantrone has been used before; The cumulative does of doxorubicin and epirubicin before inclusion have surpassed 360 mg/m2 and 600 mg/m2, respectively; Heart disease was caused after Anthracycline-based drugs used; Other antineoplastic drugs need to be used in this study; History of Anthracycline-based drug allergy or liposome drug allergy; Uncontrolled primary brain tumor or brain metastases;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mitoxantrone 12 mg/m2<br>Mitoxantrone Hydrochloride Liposome Injection 12 mg/m2 will be infused intravenously once over 1 hours in 250 ml 5％ glucose injection on the first day during a treatment phase of 3 weeks. | Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m2 will be infused intravenously once 1-2 minutes in 20-30 ml saline on the first day during a treatment phase of 3 weeks.<br>Drug: Vincristine<br>* Vincristine 0.3-0.5 mg/ml will be infused intravenously once about 5 minutes in saline on the first day during a treatment phase of 3 weeks.<br>Drug: Prednisone<br>* Prednisone 100 mg/d will be taken orally on the first 1-5 day during a treatment phase of 3 weeks.<br>|
| Experimental: Mitoxantrone 16 mg/m2<br>Mitoxantrone Hydrochloride Liposome Injection 16 mg/m2 will be infused intravenously once over 1 hours in 250 ml 5％ glucose injection on the first day during a treatment phase of 3 weeks. | Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m2 will be infused intravenously once 1-2 minutes in 20-30 ml saline on the first day during a treatment phase of 3 weeks.<br>Drug: Vincristine<br>* Vincristine 0.3-0.5 mg/ml will be infused intravenously once about 5 minutes in saline on the first day during a treatment phase of 3 weeks.<br>Drug: Prednisone<br>* Prednisone 100 mg/d will be taken orally on the first 1-5 day during a treatment phase of 3 weeks.<br>|
| Experimental: Mitoxantrone 20mg/m2<br>Mitoxantrone Hydrochloride Liposome Injection 20 mg/m2 will be infused intravenously once over 1 hours in 250 ml 5％ glucose injection on the first day during a treatment phase of 3 weeks. | Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m2 will be infused intravenously once 1-2 minutes in 20-30 ml saline on the first day during a treatment phase of 3 weeks.<br>Drug: Vincristine<br>* Vincristine 0.3-0.5 mg/ml will be infused intravenously once about 5 minutes in saline on the first day during a treatment phase of 3 weeks.<br>Drug: Prednisone<br>* Prednisone 100 mg/d will be taken orally on the first 1-5 day during a treatment phase of 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR(Objective response rate) |  | 12 Weeks |