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

Diffuse Large B Cell Lymphoma (DLBCL) Clinical Trial

— BELIEVE-01  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05234684
• Other study ID #: ICP-CL-00115
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: February 2024
• Source: Beijing InnoCare Pharma Tech Co., Ltd.
• Contact: Weili Zhao
• Phone: +86 021-64370045
• Email: zwl_trial[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 30, 2025
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma (DLBCL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Orelabrutinib + R-CHOP
The orelabrutinib is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.
• Placebo + R-CHOP
The placebo is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.

Locations

Country	Name	City	State
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Beijing Hospital	Beijing	Beijing
China	The first affiliated hospital of bengbu medical college	Bengbu	Anhui
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Chenzhou first people's Hospital	Chenzhou	Hunan
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	The Southwest Hospital of AMU	Chongqing	Chongqing
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat-sen University Cancer Center Internal medicine department	Guandong	Guangzhou
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	ZhuJiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital Zhejiang University School Of Medicine	Hangzhou	Zhejiang
China	The first affiliated Hospital Zhejiang University School Of Medicine	Hangzhou	Zhejiang
China	Anhui Provincal Cancer Hospital	Hefei	Anhui
China	Provincial Hospital Affiliated to Shandong First Medical University	Jinan	Shandong
China	Qilu Hospital Of Shandong University	Jinan	Shandong
China	Gansu Provincial Cancer Hospital	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of science and Technology	Luoyang	Henan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shanghai 6th People's Hospital	Shanghai	Shanghai
China	Shanghai Changzheng Hospital	Shanghai	Shanghai
China	Shaoxing People's Hospital	Shaoxing	Zhejiang
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	PEKING University SHENZHEN Hospital	Shenzhen	Guangdong
China	The Second Hospital of Hebei Medical University	Shijia Zhuang	Hebei
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Affiliated Cancer Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The first Affiliated Hospital Of Xi'an Jiaotong University	Xi'an	Shanxi
China	The Second Affiliated Hospital Of Xi'an Jiaotong University	Xi'an	Shanxi
China	The First Affiliated Hospital Of XIAMEN University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing InnoCare Pharma Tech Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	Progression free survival (PFS) accessed by independent review committee (IRC)	Up to 3 years and 9 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	Duration of Response (DOR)	Duration of Response (DOR) accessed by independent review committee (IRC) and investigator	Up to 3 years and 9 months
Secondary	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
Secondary	Overall survival (OS) rate	2-year overall survival (OS) rate Accessed by independent review committee (IRC) and investigator	Up to 2 years
Secondary	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