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

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

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.

Study Overview

• Status: Completed
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: CHOP combined with CMAB304; Drug: CHOP, CMAB304

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 278
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun-Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 18 to 70 year, male or female
2. Previously untreated
3. DLBCL patients with CD20-positive
4. 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
5. Normal blood test, adequate liver and renal function;
6. ECOG score 0~2
7. Life expectancy of greater than 3 months
8. No other malignancy treatment history, except cured carcinoma in situ of the cervix or squamous cell or basal cell skin cancer
9. Signed ICF

Exclusion Criteria:

1. DLBCL transformed from other low-grade NHL types
2. Primary central nervous system lymphoma, or primary gastrointestinal DLBCL
3. History of foreign protein allergies
4. Abnormal liver and/or renal function
5. Suspected or diagnosed central nervous system violation
6. Serious infection or organic diseases
7. Heart disease, heart failure, heart block above second degree, myocardial infarction occurred within six months
8. Breastfeeding or pregnant
9. Leukemia crisis or bone marrow metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination group	Drug: CHOP combined with CMAB304; 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.; Other Names: cyclophosphamide, doxorubicin, vincristine, prednisone
Experimental: sequential group	Drug: CHOP, CMAB304; 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.; Other Names: cyclophosphamide, doxorubicin, vincristine, prednisone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai CP Guojian Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Daobin Zhou, PhD, Peking Union Medical College Hospital; Principal Investigator: Weijing Zhang, PhD, Affiliated Hospital of Chinese PLA Military Academy of Medical Sciences; Principal Investigator: Yiping Zhang, PhD, Zhejiang Cancer Hospital; Principal Investigator: Jifeng Feng, PhD, Jiangsu Cancer Institute & Hospital; Principal Investigator: Yu Yang, PhD, Fujian Cancer Hospital; Principal Investigator: Qitao Yu, PhD, Cancer Hospital of Guangxi Medical University; Principal Investigator: Yuankai Shi, PhD, Cancer Institute ＆Hospital. China Academy of Medical Sciences; Principal Investigator: Lugui Qiu, PhD, Tianjin Hematonosis Hospital; Principal Investigator: Ting Liu, PhD, West China Hospital; Principal Investigator: Wenbin Qian, PhD, First Affiliated Hospital of Zhejiang University; Principal Investigator: Ping Zou, PhD, Union Hospital of Tongji Medical College of Huazhong University of Science & Technology; Study Chair: Zhongzhen Guan, PhD, Sun Yat-sen University; Study Director: Huiqiang Huang, PhD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 25, 2011
• First Posted (Estimate): October 26, 2011

Study Record Updates

• Last Update Posted (Estimate): October 26, 2011
• Last Update Submitted That Met QC Criteria: October 25, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: untreated, CD20-positive
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: 304NHL-050617