Study of Recombinant Human-Mouse Chimeric Anti-CD20 Monoclonal Antibody to Treat Non-hodgkin's Lymphoma

Study Overview
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Brief Summary
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CD20, the protein which is expressed on the surface of all mature B cells, is active in many B-cell lymphomas that express this molecule such as Diffuse Large B Cell Lymphoma (DLBCL), the most frequently occurring subtype of non-Hodgkin lymphomas. In clinical practice, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone combination chemotherapy (CHOP) is still considered one of the standard treatment to DLBCL. CMAB304(Retuxira), the chimeric monoclonal antibody is designed to targeted against CD20 for treatment of lymphoma diseases. This trial aimed to observe the safety and efficacy of CMAB304, by added CMAB304 to CHOP chemotherapy regimen compared with CHOP chemotherapy alone.

Detailed Description
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Rituximab, a chimeric anti-CD20 monoclonal antibody, has been proved valuable treatment for CD20-positive DLBCL. The combination of rituximab with CHOP has been shown to increase both survival and response rate, in comparison to CHOP alone. CMAB304(Retuxira), a biosimilar of rituximab, was developed by Shanghai CP Guojian Pharmaceutical Co.,Ltd. Previous Phase I study showed that CMAB304 was well tolerated as monotherapy and the pharmacokinetic data exhibited a non-linear profile over the dose range of 250 to 500 mg/m2. In this study, efficacy and safety of CMAB304 were evaluated in DLBCL patients.

Official Title
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An Open-labeled, Multi-center, Randomized, Prospective Phase III Study Comparing CMAB304 in Combination With CHOP to CHOP Alone With CMAB304 Maintenance in Patients With DLBCL

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: CHOP combined with CMAB304
* Drug: CHOP, CMAB304


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 70 year, male or female Previously untreated DLBCL patients with CD20-positive Lymphoma lesions can be Measured and evaluated; Spiral CT or MR evaluation of the lesion must be ≥ 1cm; Measured by clinical examination or others must be ≥ 2cm Normal blood test, adequate liver and renal function; ECOG score 0 2 Life expectancy of greater than 3 months No other malignancy treatment history, except cured carcinoma in situ of the cervix or squamous cell or basal cell skin cancer Signed ICF Exclusion Criteria: DLBCL transformed from other low-grade NHL types Primary central nervous system lymphoma, or primary gastrointestinal DLBCL History of foreign protein allergies Abnormal liver and/or renal function Suspected or diagnosed central nervous system violation Serious infection or organic diseases Heart disease, heart failure, heart block above second degree, myocardial infarction occurred within six months Breastfeeding or pregnant Leukemia crisis or bone marrow 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination group<br> | Drug: CHOP combined with CMAB304<br>* Patients treated with CHOP-304 undergo 1 cycle every 3 weeks, received CMAB304 at a dose of 375 mg/m2 on day 1 and CHOP on day 2 of each of the 6 cycles.<br>* Other names: cyclophosphamide, doxorubicin, vincristine, prednisone;|
| Experimental: sequential group<br> | Drug: CHOP, CMAB304<br>* First standard CHOP, then sequential CMAB304 in patients who reached a complete response or undocumented complete response at the end of treatment of 6 cycles.<br>* Other names: cyclophosphamide, doxorubicin, vincristine, prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate | Tumor responses were assessed after 6 cycles of CMAB304-CHOP or 6 cycles of CHOP alone and classified as CR,CRu,PR,SD or PD. | up to 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event-free survival | Events were defined as disease progression or relapse, institution of a new anticancer treatment, or death from any cause. | From date of randomization until the date of first documented progression or relapse, institution of a new anticancer treatment, or death from any cause, whichever came first, assessed up to 50 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated, CD20-positive