Orelabrutinib With R-CHOP-like Regimen for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of orelabrutinib combined with rituximab，followed by orelabrutinib combined with R-CHOP-like regimen for newly diagnosed untreated Non-GCB DLBCL Patients

Detailed Description
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The study will start with an initial 21-days of induction therapy with orelabrutinib and rituximab，following imaging examinations to evaluate response rates. Then treatment with 6 cycles chemoimmunotherapy (R-CHOP-like) either alone or in combination with orelabrutinib will depend on response during induction phase. Each cycle is 21 days.

Official Title
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A Phase 2 Study of Orelabrutinib With R-CHOP-like Regimen for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Orelabrutinib
* Biological: Rituximab
* Drug: CHOP-like Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Non-GCB DLBCL Age ≥18 and ≤70 years At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm) ECOG performance status 0-2 Lymphoma International Prognostic Score (IPI) ≥ 2 Life expectancy ≥ 6 months Adequate organ and marrow function Agreement to practice birth control from the time of enrollment until the follow-up period of the study Exclusion Criteria: Received major surgery within 4 weeks before treatment or existed unhealed wounds or ulcers, except biopsy related to lymphoma diagnosis All patients with primary central nervous system lymphoma History of stroke or intracranial hemorrhage within 6 months before screening, require or receive anticoagulant therapy with warfarin or an equivalent antagonist Requires treatment with strong /moderate CYP3A inhibitors or inducers Uncontrolled comorbidity or complications, including but not limited to: symptomatic congestive heart failure (New York Heart Association Class III-IV) or symptomatic or poorly controlled arrhythmias and/or significant pulmonary disease HIV infection and/or active hepatitis B or active hepatitis C infection Uncontrolled active systemic infection Known hypersensitivity or contraindications to any drug involved in the study Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib+R-CHOP-like<br>Orelabrutinib plus Rituximab for 21 days; Following Imaging examinations, patients with ≥25% tumor reduction, treat with orelabrutinib 150mg qd orally plus R-CHOP-like for 6 cycles; whereas, patients with <25% tumor reduction, withdraw from the study，treat with R-CHOP-like alone for 6 cycle | Drug: Orelabrutinib<br>* Orelabrutinib 150mg qd PO<br>Biological: Rituximab<br>* Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle<br>Drug: CHOP-like Regimen<br>* cyclophosphamide, anthracene nucleus chemotherapeutics（doxorubicin，liposomal doxorubicin, etc.）, vinca alkaloids（vincristine, vindesine, etc.），and glucocorticoid （dexamethasone，prednison, etc.）.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The rate of patients who achieved complete response after treatment by OR-CHOP-like | At the end of Cycle 6（each cycle is 21 days） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | The rate of patients who achieved CR or PR after treatment by OR-CHOP-like | At the end of Cycle 3 and Cycle 6（each cycle is 21 days） | 
| Progression-free survival（PFS） | PFS will be assessed from the first OR(Orelabrutinib plus Rituximab) given to date of progression, relapse, death or end of follow-up | up to 24 month after the end of last patient's treatment | 
| Incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events | The safety and tolerability of the therapeutic regimen measured by the incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events | initiation of study drug until 30 days after last dose | 
| Mini response rate | The rate of patients who achieve ≥25% tumor reduction after OR treatment | the first 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Orelabrutinib