Zanubrutinib Plus R-CHOP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Study Overview
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Brief Summary
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Aim of this study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients

Detailed Description
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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of DLBCL was non-GCB subtype DLBCL.The non-GCB DLBCL revealed poor clinical outcomes. Bruton's tyrosine kinase (BTK) inhibitors have established therapeutic activity in B cell malignancies, with potential activity in non-GCB DLBCL. This study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients.

Official Title
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Zanubrutinib Combination With R-CHOP in Treating Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Conditions
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Non-GCB/ABC Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Non-GCB DLBCL with extrinsic involvement Age ≥ 18 years Measurable disease of at least 15mm(node)/10mm（extranodal） ECOG performance status 0-2 Adequate organ function:Cardiac ejection fraction (EF) ≥ 50%;Creatinine clearance rate (≥30 mL/min) of serum creatinine; Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) ≤3 times ULN Adequate bone marrow function:Platelet count (≥ 50×10^9/L);Hemoglobin (≥ 8 g/dL);The absolute value of neutrophils (≥1.0×10^9/L) Estimated survival time ≥3 months Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study Exclusion Criteria: Accepted major surgery within 4 weeks before treatment; Diagnosis of primary mediastinal lymphoma or primary CNS lymphoma; Previous history of indolent lymphoma; Prior malignancy (other than DLBCL), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer 、malignant tonsilloma or carcinoma in situ; History of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists; Requires treatment with a strong/medium CYP3A inducer; The previous use of anthracycline-based drugs > 150 mg/m2; Evidence of complications or medical conditions, including but not limited, that may interfere the conduct of the study or place the patient at serious risk:significant cardiovascular disease(class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification、myocardial infarction within 6 months of screening、uncontrolled or symptomatic arrhythmias) and/or significant lung disease; HIV infection and/or active hepatitis B or active hepatitis C; Uncontrolled systemic infection; Pregnant or breasting-feeding women; According to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.

Ages Eligible for Study
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Minimum Age: 18 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: R-CHOP + Zanubrutinib<br>Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) | Drug: Zanubrutinib<br>* Zanubrutinib-160mg bid PO d0-d20(1-21d)<br>* Other names: BTK inhibitors;Drug: Rituximab<br>* Rituximab-375 mg/m2 i.v d0 (/21d)<br>* Other names: MabThera;Drug: Cyclophosphamide<br>* Cyclophosphamide-750 mg/m2 i.v d1 (/21d)<br>* Other names: CTX;Drug: Doxorubicin<br>* Doxorubicin-50 mg/m2 i.v d1 (/21d)<br>* Other names: ADM;Drug: Vincristine<br>* Vincristine-1.4 mg/m2 i.v d1 (/21d)(2 mg max)<br>* Other names: VCR;Drug: Prednisone<br>* Prednisone-100 mg p.o d1-d5 (/21d)<br>* Other names: Prednisonum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival(PFS) | To measure the duration of response to ZR-CHOP over a follow-up period of 18 months | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | To measure the duration of response to ZR-CHOP over a follow-up period of 18 months | up to 18 months | 
| Complete Response Rate | Number of patients who achieved complete response after treatment by ZR-CHOP | up to 18 months | 
| Duration of Response | Duration of overall response will be assessed from the first ZR-CHOP given to progression,death or last follow-up. | up to 18 months | 
| Overall Survival | OS will be assessed from the first ZR-CHOP given to death or last follow-up. | up to 18 months | 
| Adverse events profile | Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated | Measured from start of treatment until 28 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zanubrutinib, R-CHOP, Newly diagnosed Non-GCB DLBCL