polatuzumab vedotin and zanubrutinib plus r-chp for patients with newly diagnosed untreated non-gcb dlbcl

Conditions: Effects of Chemotherapy; Safety Issues

Summary: aim of this study will evaluate the efficacy and safety of polatuzumab vedotin and zanubrutinib in combination with r-chp for newly diagnosed untreated non-gcb dlbcl patients with extranodal involvement.

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. the polarix study also observed an benefit in the efficacy of polatuzumab vedotin in first-line treatment of dlbcl patients. this study will evaluate the efficacy and safety of polatuzumab vedotin and zanubrutinib in combination with r-chp for newly diagnosed untreated non-gcb dlbcl patients with extranodal involvement.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed non-gcb dlbcl with extrinsic involvement； 2. measurable disease of at least 15mm(node)/10mm（extranodal）； 3. ecog performance status 0-2； 4. 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； 5. adequate bone marrow function:platelet count (≥ 50×10\^9/l);hemoglobin (≥ 8 g/dl);the absolute value of neutrophils (≥1.0×10\^9/l) 6. estimated survival time ≥3 months 7. 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: 1. accepted major surgery within 4 weeks before treatment; 2. diagnosis of primary mediastinal lymphoma or primary cns lymphoma; 3. previous history of indolent lymphoma; 4. 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; 5. history of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists; 6. requires treatment with a strong/medium cyp3a inducer; 7. the previous use of anthracycline-based drugs \> 150 mg/m2; 8. 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; 9. hiv infection and/or active hepatitis b or active hepatitis c; 10. uncontrolled systemic infection; 11. pregnant or breasting-feeding women; 12. according to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.