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

Phase 3

Recruiting

• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Interventions: Drug: Placebo + R-CHOP; Drug: Orelabrutinib + R-CHOP

• Registration Number: NCT05234684
• Lead Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-29
• Study First Submitted QC: 2022-02-08
• Study First Posted: 2022-02-10
• Study Start: 2022-11-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-07
• Primary Completion: 2024-07-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo+ R-CHOP	Placebo + R-CHOP	Participants will receive 150 mg placebo once daily with R-CHOP on day 1 of each cycle (21 days).
Orelabrutinib+ R-CHOP	Orelabrutinib + R-CHOP	Participants will receive 150 mg of oral orelabrutinib once daily with R-CHOP on day 1 of each cycle (21 days).

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (44)

The first affiliated hospital of bengbu medical college; 🇨🇳 Bengbu, Anhui, China

Anhui Provincal Cancer Hospital; 🇨🇳 Hefei, Anhui, China

Beijing Hospital; 🇨🇳 Beijing, Beijing, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China

The Southwest Hospital of AMU; 🇨🇳 Chongqing, Chongqing, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

The First Affiliated Hospital Of XIAMEN University; 🇨🇳 Xiamen, Fujian, China

Gansu Provincial Cancer Hospital; 🇨🇳 Lanzhou, Gansu, China

The First People's Hospital of Foshan; 🇨🇳 Foshan, Guangdong, China

Guangdong General Hospital; 🇨🇳 Guangzhou, Guangdong, China

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