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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diffuse Large B Cell Lymphoma (DLBCL)

Intervention / Treatment
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* Drug: Orelabrutinib + R-CHOP
* Drug: Placebo + R-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18 and 80 years old Treatment-naive patients Histologically confirmed diffuse large B-cell lymphoma (DLBCL) and CD20 positive. Provide FFPE slices of past or fresh tumor biopsy tissue. At least one measurable lesion. Lymphoma International Prognostic Score (IPI) ≥ 2. Ann Arbor stage II-IV, or stage I with bulky lesion (diameter > 7.5 cm） ECOG PS score of 0-2 Subjects who in line with the testing standard of the clinical trial laboratory. Life expectancy ≥ 6 months. Able to provide signed written informed consent. Exclusion Criteria: History of other active malignancies within 5 years of study entry, unless cured without evidence of relapse or metastasis Lymphoma involving the central nervous system or leptomeningeal metastasis. Transformed lymphoma, that is transformed from other types of lymphoma. Primary mediastinal large B-cell lymphoma. History of stroke or intracranial hemorrhage within 6 months before screening. 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. 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. 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). Administer live and attenuated vaccines (semi-inactivated) within 28 days prior to first receiving the test drug. Planned stem cell transplant during the experimental treatment are excluded. 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. Current diagnosis of any mental or cognitive impairment, drug abuse, or alcohol abuse. 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 The last use of CYP3A inhibitor or CYP3A inducer is less than 5 half-lives from 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |