A Study of Orelabrutinib Plus R-CHOP in Treatment-naïve Patients With MCD Subtype Diffuse Large B-cell Lymphoma (BELIEVE-01)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Orelabrutinib Plus R-CHOP Versus Placebo Plus R-CHOP in Treatment-naïve Patients With MCD Subtype DLBCL

The purpose of this study is to evaluate the safety and efficacy of orelabrutinib combined with R-CHOP regimen versus placebo with R-CHOP in the treatment of treatment-naïve patients with MCD subtype DLBCL.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: Orelabrutinib + R-CHOP; Drug: Placebo + R-CHOP

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: +86 021-64370045; Email: zwl_trial@163.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical College
      • Contact: Yanli Yang
    • Hefei, Anhui, China, 230031
      • Recruiting
      • Anhui Provincal Cancer Hospital
      • Contact: Kaiyang Ding
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Beijing Hospital
      • Contact: Hui Liu
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Chongqing University Cancer Hospital
      • Contact: Yingyu Nan
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • The Southwest Hospital of Amu
      • Contact: Shuangnian Xu
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: Jianzhen Shen
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Bing Xu
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Recruiting
      • Gansu Provincial Cancer Hospital
      • Contact: Jie Cui
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Recruiting
      • The First People's Hospital of Foshan
      • Contact: Ying Zhao
    • Guangzhou, Guangdong, China, 510280
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
      • Contact: Shaojie Wu
    • Guangzhou, Guangdong, China, 510700
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: chunkang Chang
    • Guangzhou, Guangdong, China, 510180
      • Recruiting
      • Guangdong General Hospital
      • Contact: Wenyu Li
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Hongyu Zhang
  • Guangzhou
    • Guandong, Guangzhou, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center Internal medicine department
      • Contact: Qingqing Cai
  • Hebei
    • Baoding, Hebei, China, 050031
      • Recruiting
      • Affiliated Hospital of Hebei University
      • Contact: hua xue
    • Shijia Zhuang, Hebei, China, 050000
      • Recruiting
      • The Second Hospital of Hebei Medical University
      • Contact: jinhai Ren
  • Henan
    • Luoyang, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Ling Qin
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Keshu Zhou
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Xinhua Wang
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Liang Huang
    • Wuhan, Hubei, China, 430023
      • Recruiting
      • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Liling Zhang
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Hui Zhou
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The Second Xiangya Hospital of Central South University
      • Contact: Hongling Peng
    • Chenzhou, Hunan, China, 423099
      • Recruiting
      • Chenzhou First People's Hospital
      • Contact: Xinquan Liang
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • The Affiliated Hospital of Nanjing University Medical School
      • Contact: Jingyan Xu
    • Wuxi, Jiangsu, China, 214043
      • Recruiting
      • Wuxi People's Hospital
      • Contact: Xin Zhou
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Fei Li
    • Nanchang, Jiangxi, China, 330001
      • Recruiting
      • Jiangxi Cancer Hospital
      • Contact: Wuping Li
  • Liaoning
    • Dalian, Liaoning, China, 116023
      • Recruiting
      • The Second Hospital of Dalian Medical University
      • Contact: Xiuhua Sun
    • Shenyang, Liaoning, China, 110002
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: xiaojing Yan
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Ming Hou
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Provincial Hospital Affiliated to Shandong First Medical University
      • Contact: Xin Wang
    • Qingdao, Shandong, China, 266400
      • Recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: Hongwei Xue
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
      • Contact: Weili Zhao; Email: zwl_trial@163.com
    • Shanghai, Shanghai, China, 200003
      • Active, not recruiting
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China, 201306
      • Active, not recruiting
      • Shanghai 6th People's Hospital
  • Shanxi
    • Xi'an, Shanxi, China, 710004
      • Recruiting
      • The Second Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Aili He
    • Xi'an, Shanxi, China, 710004
      • Active, not recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Active, not recruiting
      • West China Hospital Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Cancer Hospital
      • Contact: Zhengzi Qian
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Recruiting
      • Affiliated Cancer Hospital of Xinjiang Medical University
      • Contact: Shujuan Wen
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Recruiting
      • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
      • Contact: Jin Zhang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital Zhejiang University School of Medicine
      • Contact: Jie Jin
    • Shaoxing, Zhejiang, China, 312000
      • Recruiting
      • Shaoxing People's Hospital
      • Contact: Jiaping Fu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women between 18 and 80 years old
2. Treatment-naive patients
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) and CD20 positive.
4. Provide FFPE slices of past or fresh tumor biopsy tissue.
5. At least one measurable lesion.
6. Lymphoma International Prognostic Score (IPI) ≥ 2.
7. Ann Arbor stage II-IV, or stage I with bulky lesion (diameter > 7.5 cm）
8. ECOG PS score of 0-2
9. Subjects who in line with the testing standard of the clinical trial laboratory.
10. Life expectancy ≥ 6 months.
11. Able to provide signed written informed consent.

Exclusion Criteria:

1. History of other active malignancies within 5 years of study entry, unless cured without evidence of relapse or metastasis
2. Lymphoma involving the central nervous system or leptomeningeal metastasis.
3. Transformed lymphoma, that is transformed from other types of lymphoma.
4. Primary mediastinal large B-cell lymphoma.
5. History of stroke or intracranial hemorrhage within 6 months before screening.
6. Co-morbidity of uncontrolled or significant cardiovascular disease, significant impaired lung function, significant gastrointestinal abnormalities, uncontrolled infections (including HBV, HCV, HIV/AIDS and tuberculosis), or active autoimmune disease.
7. Active bleeding within 2 months before screening, or a clear bleeding tendency determined by the investigator; a history of deep vein thrombosis or pulmonary embolism.
8. Previous history of surgeries (major 4 weeks and minor 2 weeks prior screening) , organ transplant or hematopoietic stem cell transplantation, or progressive multifocal leukoencephalopathy (PML).
9. Administer live and attenuated vaccines (semi-inactivated) within 28 days prior to first receiving the test drug.
10. Planned stem cell transplant during the experimental treatment are excluded.
11. Chemotherapy, immunotherapy, targeted therapy, radiotherapy, or traditional Chinese medicine with anti-tumor effects for the purpose of anti-tumor therapy within 4 weeks before starting to take the experimental drug. Excluding short-term emergency use of corticosteroids before treatment.
12. Current diagnosis of any mental or cognitive impairment, drug abuse, or alcohol abuse.
13. Pregnant, lactating women, or women at childbearing ages who will not use contraception during the study up to 12 months after the last dose of rituximab or 180 days after the last dose of study drug
14. The last use of strong CYP3A inhibitor or strong CYP3A inducer is less than 5 halflivesfrom the first trial drug, or the drug or food with moderate and strong CYP3A inhibitory effect or strong CYP3A induction effect is planned to be taken at the same time during this study.
15. Any serious medical condition that, in the investigator's opinion, would put the subject at unacceptable risk and/or would prevent the subject from signing the informed consent form. In the opinion of the investigator, the subject's participation in the study would be at unacceptable risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orelabrutinib+ R-CHOP; Participants will receive 150 mg of oral orelabrutinib once daily with R-CHOP on day 1 of each cycle (21 days).	Drug: Orelabrutinib + R-CHOP; The orelabrutinib is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.; Other Names: ICP-022+ R-CHOP
Placebo Comparator: Placebo+ R-CHOP; Participants will receive 150 mg placebo once daily with R-CHOP on day 1 of each cycle (21 days).	Drug: Placebo + R-CHOP; The placebo is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression free survival (PFS) accessed by independent review committee (IRC)	Up to 3 years and 9 months
Complete response rate (CRR) by independent review committee (IRC)	Complete response rate (CRR) at the completion of combination therapy accessed by independent review committee (IRC)	Up to 3 years and 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR) by investigator	Complete response rate (CRR) at the completion of combination therapy accessed by investigator	Up to 3 years and 9 months
Overall response rate (ORR) by independent review committee (IRC) and investigator	Overall response rate (ORR) accessed by independent review committee (IRC) and investigator	Up to 3 years and 9 months
Overall response rate (ORR) at the completion of combination therapy by independent review committee (IRC) and investigator	Overall response rate (ORR) at the completion of combination therapy accessed by independent review committee (IRC) and investigator	Up to 3 years and 9 months
Duration of Response (DOR)	Duration of Response (DOR) accessed by independent review committee (IRC) and investigator	Up to 3 years and 9 months
Disease free survival (DFS) rate and event free survival (EFS) rate	2-year disease free survival (DFS) rate and 2-year event free survival (EFS) rate	Up to 2 years
Overall survival (OS) rate	2-year overall survival (OS) rate Accessed by independent review committee (IRC) and investigator	Up to 2 years
Occurrence of adverse events and serious adverse events according to CTCAE V5.0.	The safety of Orelabrutinib measured by the occurrence of adverse events and serious adverse events according to CTCAE V5.0.	Up to 3 years and 9 months

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
• Investigators: Principal Investigator: Weili Zhao, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Estimated): July 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 29, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; 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; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: ICP-CL-00115

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No