Clinical trial NCT06468943: 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.
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Effects of Chemotherapy
Safety Issues
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-06-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

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.

Primary outcomes:
measure: Progression-free Survival（PFS）
timeFrame: 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 outcomes:
measure: Objective Response rate（ORR）
timeFrame: 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.
measure: Complete Response（CR）
timeFrame: 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.
measure: Duration of Response（DOR）
timeFrame: All time in the study
measure: Overall Survival
timeFrame: 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.
measure: Adverse Events(AEs)
timeFrame: 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.
Other outcomes:
measure: Exploratory study endpoint
timeFrame: 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.
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Nanjing
Study officials:
References: