Clinical trial NCT03777085: Study of TQB2303 in Patients With CD20-Positive Diffuse Large B-cell Lymphoma (DLBCL)
Official title: Multicenter, Randomized, Double-blind, Parallel Controlled, Phase III Clinical Study to Compare the Efficacy and Safety of TQB2303 in Conbination With CHOP Regimen (T-CHOP) Versus Rituximab in Combination With CHOP Regimen (R-CHOP) in Previously Untreated Subjects With CD20-Positive Diffuse Large B-cell Lymphoma (DLBCL)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-17
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Purpose of This Study is to Compare the Efficacy, Safety, Immunogenicity and Pharmacokinetics between TQB2303 and Rituximab in Combination With CHOP in Previously Untreated Patients with Diffuse Large B-cell Lymphoma


Eligibility criteria: Inclusion Criteria:

1. Untreated CD20-positive DLBCL patients confirmed by histopathology or cytology.
2. 18 years to 75 years; Male or female patients.
3. International Prognostic Index (IPI) score of 0 to 2.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. More than 6 months life expectancy judged by the researchers.
6. At least one measurable lesions: for nodal tumor mass, more than 1.5 cm in the long axis and more than 1.0 cm in the short axis; for extranodal tumor mass, more than 1.0 cm in the long axis.
7. left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography greater than or equal to 50%.
8. Adequate hematologic function, no matter the bone marrow was attacked or not, as follows:absolute neutrophil count (ANC) ≥1.5×10\^9/L and platelet count≥75×\^9/L.
9. Understood and Signed an informed consent form.

Exclusion Criteria:

1. Known allergic reactions against human or murine monoclonal antibody, murine products, or foreign proteins.
2. Known allergic reactions against any component of CHOP regimen.
3. Previous treatment for DLBCL, including chemotherapy, immunotherapy, partial radiotherapy for lymphoma, or surgical treatment (excluding tumor mass biopsies and surgical resection for non-lymphoma lesions), or prior use of any monoclonal antibody within 3 month.
4. T-cell/histiocyte-rich large B-cell lymphoma, Primary DLBCL of the CNS, Primary cutaneous DLBCL, leg type, EBV-positive DLBCL of the elderly (EBV + DLBCL), EBV-positive DLBCL of the elderly (EBV + DLBCL), DLBCL associated with chronic infammation, Lymphomatoid granulomatosis, Primary mediastinal (thymic) large B-cell lymphoma (PMBL), ALK-positive large B-cell lymphoma, ALK-positive large B-cell lymphoma, ALK-positive large B-cell lymphoma, high-grade B-cell lymphoma (high-grade B-cell lymphoma with MYC, with or without concurrent in BCL2 and/or BCL6 gene rearrangements, high-grade B-cell lymphoma, NOS), B-cell lymphoma, Not categorizable, Characteristics between DLBCL and classical Hodgkin's lymphoma, transformed DLBCL, DLBCL secondary central nervous system invasion;
5. Other malignant tumors that have been or are currently suffering (healed skin basal cell carcinoma or cutaneous squamous cell carcinoma, or cutaneous melanoma or cervical carcinoma in situ).
6. Significantly poorly controlled diseases that can affect adherence to the study protocol, such as severe cardiovascular disease (such as the New York Heart Association class III or IV heart disease, myocardial infarction or unstable arrhythmia in the last 6 months or Unstable angina, severe hypertension, peripheral nervous system or central nervous system disease;
7. Patients with a history of progressive multifocal leukoencephalopathy.
8. Continuous corticosteroid treatment being received, dose \>30 mg/day prednisone or equivalent dose of corticosteroids ≥10 days.
9. Participation in another interventional clinical trial in the past 3 months.
10. Patients who received or underwent major surgeries within 28 days prior to enrollment, or patients with unsurgical wounds.
11. Treated with transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to enrollment.
12. Vaccination within 28 days or planned prior to enrollment.
13. Appearing the following laboratory abnormal values.

    1. Coagulation function: partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) or international normalized ratio (INR) \> 1.5 times ULN without anticoagulant therapy.
    2. Liver function: total bilirubin (TBIL) \> 1.5 times the upper limit of normal (3 times the upper limit of normal value when the liver is invaded), alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal value (\>5 times the upper limit of normal value when the liver is invaded)
    3. Renal function: serum creatinine (Cr) \> 1.5 times the upper limit of normal value.
14. an active infection at the time of enrollment, or any major infection events that affected the enrollment of the subjects determined by the investigator within 28 days (except for neoplastic fever).
15. Suspected active or latent tuberculosis infections.
16. HBsAg positive and/or HBcAb positive and HBV DNA positive.
17. HCV antibody and HCV-RNA positive; or HIV positive patients.
18. Pregnancy or breast feeding. Companion for women of childbearing age or women of childbearing age,who reluctant to take appropriate contraceptive methods within one year after the last treatment of the study;Pregnancy before pregnancy screening, the women who blood / urine results were positive.
19. Patients that researchers deem as not appropriate to enter the study.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 18 weeks
Secondary outcomes:
measure: Objective Response Rate (CR+CRu)
timeFrame: 18 weeks
measure: Progression-free survival (PFS)
timeFrame: 18 weeks
measure: Event-free survival (EFS)
timeFrame: 18 weeks
measure: Duration of Response (DOR)
timeFrame: 18 weeks
measure: :Overall survival (OS)
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Haerbin
country: China
facility: No.150 Haping Road, Nangang District
state: Heilongjiang
city: Nanjing
country: China
facility: No. 42 Baiziting Road, Xuanwu District
state: Jiangsu
city: Baoji
country: China
facility: No.8 Jiangtan Road,Weibin District
city: Changsha
country: China
facility: No. 87 Xiangya Road Furong District
city: Changsha
country: China
facility: No.138 Tongzipo Road Yuelu District
city: Changsha
country: China
facility: No.139 Renmin Middle Road Furong District
city: Chengdu
country: China
facility: No. 37 Guoxue Lane Wuhou District
city: Chengdu
country: China
facility: No. 55 Section 4 Renmin South Road Wuhou District
city: Chongqing
country: China
facility: No. 10 Daping Yangtze River Branch Road Yuzhong District
city: Chongqing
country: China
facility: No.183 Xinqiao Main Street Shapingba District
city: Fuzhou
country: China
facility: No.420 Fuma Road, Jin'an district
city: Kunming
country: China
facility: No.295 Xichang Road, Wuhua District
city: Lanzhou
country: China
facility: No. 701 Donggang Road (West) Chengguan District
city: Lanzhou
country: China
facility: No. 82 Cuiyingmen Chengguan District
city: Lanzhou
country: China
facility: No.333 Nanbinhe Middle Road Qilihe District
city: Liuzhou
country: China
facility: No. 8 Wenchang Road Chengzhong District
city: Nanchang
country: China
facility: No.519 Beijing East Road High - tech District
city: Nanning
country: China
facility: No.71 Embankment Road, Qingxiu District
city: Nantong
country: China
facility: No.20 Xisi Road Chongchuan District
city: Qingdao
country: China
facility: No.1677 Wutai Mountain Road Huangdao District
city: Weifang
country: China
facility: No. 151 Guangwen Street Kuiwen District
city: Weihai
country: China
facility: No. 3, West Mt. East Road, Wendeng District, Weihai City
city: Wuhan
country: China
facility: No. 1277 Jiefang Avenue Jianghan District
city: Wulumuqi
country: China
facility: No 137 Carp mountain Road New district
city: Wuwei
country: China
facility: No.31 Hygienic Lane Haizang Road Liangzhou District
city: Xian
country: China
facility: No. 15 West ChangLe Road New City District
city: Xian
country: China
facility: No.256 Youyi West Road Beilin District
city: Zhengzhou
country: China
facility: No. 7 Weiwu Road Jinshui District
city: Zhengzhou
country: China
facility: No.1 Jianshe East Road Erqi District
city: Zhengzhou
country: China
facility: No.127 Dongming Road, Jinshuii District
city: Zibo
country: China
facility: No. 54 Communist Youth League Road Zhangdian District
Study officials:
References: