Pharmacokinetics, Efficacy and Safety of the 304 Injection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic of the experimental drug 304 injection compared with rituximab injection in patients with CD20 positive B-cell non-Hodgkin lymphoma who had previously achieved CR/CRu status but had not deteriorated or relapsed. While to assess the safety and efficacy of the experimental drug 304 injection compared with rituximab injection.

Detailed Description
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This is a multi-center, randomized, double-blind, parallel controlled, single-dose study to evaluate the pharmacokinetic, safety and efficacy of 304 injection compared with rituximab injection. To avoid the impact of tumor burden on pharmacokinetics, this study will be conducted in CD20 positive B-cell non-Hodgkin lymphoma patients who have achieved CR/CRu status and have not yet deteriorated or relapsed. All patients will be randomly averagely entered into the experimental group and the control group.

Official Title
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A Study of Pharmacokinetics, Efficacy, and Safety of 304 Injection Compared With Rituximab in B Cell Non-Hodgkin's Lymphoma

Conditions
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CD20 Positive B Cell NHL

Intervention / Treatment
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* Drug: 304 injection
* Drug: rituximab injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological examination confirmed CD20-positive B-cell non-Hodgkin's lymphoma patients (according to WHO 2008 lymphoid tissue tumor type, and a corresponding medical history basis); Previous treatments with CR/CRu (see Appendix 1 for lymphoma efficacy criteria) and those with CD20-positive B-cell non-Hodgkin's lymphoma who have not yet worsened and relapsed believe that they can benefit from anti-CD20 monoclonal antibody therapy. The diagnosis of CRu requires complete raw data (using CT findings. The preferred enhanced CT examination) At the time of enrollment, the Eastern Oncology Cooperative Group (ECOG) had a physical status score of ≤1 (see Appendix 2 for the evaluation criteria for the ECOG physical status score) and the expected survival period was more than four months In the screening test, WBC≥3×109/L, HGB≥80g/L, ANC≥1.5×109/L, PLT≥75×109/L, left ventricular ejection fraction (LVEF) ) ≥ 50% Female patients of childbearing age were negative for the blood pregnancy test during the screening period. Patients of childbearing age are willing to contraception after signing the informed consent form until 6 months after the end of the study treatment, including but not limited to: hormonal contraception, or physical contraception, or abstinence Be able to understand and comply with clinical trial protocol requirements and voluntarily sign written informed consent Exclusion Criteria: In the past 5 years, there have been other medical history of malignant tumors (except for local malignant tumors that have been cured, such as cutaneous basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or breast carcinoma in situ) Those who have used chemotherapy drugs within 4 weeks before enrollment The clinical half-life of more than 5 drugs after taking other clinical trials in three months or other clinical trials (whichever is longer) The last time you used rituximab or other anti-CD20 mAbs for no more than 4 months In the screening test, the liver and kidney function tests have any of the following abnormalities: total bilirubin > 1.5 times the upper limit of normal, ALT > 2.5 times the upper limit of normal, AST > 2.5 times the upper limit of normal, ALP > 2.5 times the upper limit of normal, Blood Cr>1.5 times the upper limit of normal value Hyperthyroidism He was transfused within 2 weeks before enrollment, or hematopoietic cytokine therapy, such as granulocyte colony-stimulating factor (G-CSF), thrombopoietin, erythropoietin, etc. Those who were vaccinated or planned to vaccinate (attenuate) live virus vaccine within 4 weeks prior to enrollment; Oversized surgery (not including diagnostic surgery) in the past 8 weeks; Have evidence or history of central nervous system involvement or cranial neuropathy; Treponema pallidum antibody positive, or HIV antibody positive, or HCV antibody positive; HBV examination showed one of the following results: a, HBsAg positive; b, although HBsAg negative, but anti-HBc positive and peripheral blood HBV DNA titer can be measured; Have had herpes zoster and have sequelae or latent infections; Patients with a history of severe heart disease, including but not limited to: New York Heart Association NYHA class II-IV heart failure (see Appendix 3 for NYHA heart failure grading), uncontrolled angina or arrhythmia, heart conduction above II Blocking, myocardial infarction occurred within 6 months Serious illnesses that have been or are currently suffering from any other organ or system (including but not limited to: severely active infections, uncontrolled diabetes, uncontrolled hypertension/hypotension, cerebrovascular disease, gastric ulcers, respiratory diseases, activities) Sexual autoimmune diseases, etc.; and any other medical history that the subject judges to be unsuitable for participating in the trial; Pregnant or lactating female subjects, or those who are unwilling to contraception during the trial Severe allergies, or any component known to be rituximab or other anti-CD20 mAbs or allergic to murine proteins; Subjects had a history of drug abuse or a history of smoking and drinking during the first 6 months of enrollment; The investigator judged that the patient was not suitable for entering any other circumstances of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>304 injection.WILL be administered single dose IV in the patients with CD20 positive B cell NHL | Drug: 304 injection<br>* Monoclonal antibodies, 100mg/10ml per injection<br>|
| Active Comparator: control group<br>Rituximab will be administered single dose IV in the patients with CD20 positive B cell NHL. | Drug: rituximab injection<br>* 100mg/10ml per injection ，manufactured by Roche<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC [0-t] | To assess PK parameter of plasma 304 or rituximab: Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t]) | For 85 days | 
| AUC [0-∞] | To assess PK parameter of plasma 304 or rituximab: Area under the concentration-time curve from time zero extrapolated to infinity (AUC [0-∞]) | For 85 days | 
| Cmax | To assess PK parameter of plasma 304 or rituximab：Observed maximum plasma concentration (Cmax) | For 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax | To assess PK parameter of plasma 304 or rituximab：Time to Cmax (tmax) | For 85 days | 
| t1/2 | To assess PK parameter of plasma 304 or rituximab：Elimination half-life (t1/2) | For 85 days | 
| MRT | To assess PK parameter of plasma 304 or rituximab：Mean residence time (MRT) | For 85 days | 
| Vz | To assess PK parameter of plasma 304 or rituximab：Apparent volume of distribution(Vz) | For 85 days | 
| CLz | To assess PK parameter of plasma 304 or rituximab：apparent clearance (CLz) | For 85 days | 
| ADA | To evaluate the incidence of anti-304 and anti-rituximab antibodies | Up to 9 months | 
| Adverse events | To evaluate the adverse events (incidence, severity, outcome, causality with the investigational drug, etc.). | Up to 85 days |