Polatuzumab Vedotin and Zanubrutinib Plus R-CHP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Official title

Polatuzumab Vedotin and Zanubrutinib Plus R-CHP for Patients in Treatment of Newly Diagnosed Untreated Non-GCB DLBCL With Extranodal Involvement.

Overview

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.

Detailed description

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.

Interventions

• Drug Polatuzumab Vedotin
  1.8mg/kg/21d（d0） Intravenous infusion
• Drug Zanubrutinib
  160mg bid PO（d0-d20）
• Drug Rituximab
  375mg/㎡/21d（d0） Intravenous infusion
• Drug Cyclophosphamide
  750mg/㎡/21d（d1） Intravenous infusion
• Drug Doxorubicin
  50mg/㎡/21d（d1） Intravenous infusion
• Drug Prednisone
  100mg PO （d1-d5）/21d

Primary outcome measures

• Progression-free Survival（PFS） [Time frame: From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.]

Secondary outcome measures (5)

• Objective Response rate（ORR） [Time frame: From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.]
• Complete Response（CR） [Time frame: From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.]
• Duration of Response（DOR） [Time frame: All time in the study]
• Overall Survival [Time frame: From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.]
• Adverse Events(AEs) [Time frame: From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.]

Eligibility criteria

Inclusion criteria

• Histologically confirmed Non-GCB DLBCL with extrinsic involvement；
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Identifiers

NCT: NCT06468943 · Pola-ZR-CHP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗