Clinical trial NCT05234684: A Study of Orelabrutinib Plus R-CHOP in Treatment-naïve Patients With MCD Subtype Diffuse Large B-cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 3 years and 9 months
measure: Complete response rate (CRR) by independent review committee (IRC)
timeFrame: Up to 3 years and 9 months
Secondary outcomes:
measure: Complete response rate (CRR) by investigator
timeFrame: Up to 3 years and 9 months
measure: Overall response rate (ORR) by independent review committee (IRC) and investigator
timeFrame: Up to 3 years and 9 months
measure: Overall response rate (ORR) at the completion of combination therapy by independent review committee (IRC) and investigator
timeFrame: Up to 3 years and 9 months
measure: Duration of Response (DOR)
timeFrame: Up to 3 years and 9 months
measure: Disease free survival (DFS) rate and event free survival (EFS) rate
timeFrame: Up to 2 years
measure: Overall survival (OS) rate
timeFrame: Up to 2 years
measure: Occurrence of adverse events and serious adverse events according to CTCAE V5.0.
timeFrame: Up to 3 years and 9 months
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Hefei
country: China
facility: Anhui Provincal Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The Southwest Hospital of AMU
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital Of XIAMEN University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: PEKING University SHENZHEN Hospital
state: Guangdong
city: Guandong
country: China
facility: Sun Yat-sen University Cancer Center Internal medicine department
state: Guangzhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Shijia Zhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou first people's Hospital
state: Hunan
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital Of Shandong University
state: Shandong
city: Jinan
country: China
facility: Provincial Hospital Affiliated to Shandong First Medical University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai 6th People's Hospital
state: Shanghai
city: Xi'an
country: China
facility: The first Affiliated Hospital Of Xi'an Jiaotong University
state: Shanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital Of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The first affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School Of Medicine
state: Zhejiang
city: Shaoxing
country: China
facility: Shaoxing People's Hospital
state: Zhejiang
Study officials:
affiliation: Ruijin Hospital
name: Weili Zhao
role: PRINCIPAL_INVESTIGATOR
References: