Effects of Chemotherapy, Safety Issues
Conditions
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.
Interventions
DRUGPolatuzumab Vedotin
1.8mg/kg/21d（d0） Intravenous infusion
DRUGZanubrutinib
160mg bid PO（d0-d20）
DRUGRituximab
375mg/㎡/21d（d0） Intravenous infusion
DRUGCyclophosphamide
750mg/㎡/21d（d1） Intravenous infusion
DRUGDoxorubicin
50mg/㎡/21d（d1） Intravenous infusion
DRUGPrednisone
100mg PO （d1-d5）/21d
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival（PFS） | 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. | The time between enrollment and tumor occurrence (in any aspect) progression or (for any reason) death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response rate（ORR） | 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. | The proportion of patients who achieved complete or partial response in efficacy evaluation at the end of treatment |
| Complete Response（CR） | 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. | The proportion of patients who achieved complete response in efficacy evaluation at the end of treatment |
| Overall Survival | 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. | The time between enrollment to death(for any reason) . |
| Adverse Events(AEs) | 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. | All treatment-related adverse events that occur during patient treatment and follow-up. |
| Duration of Response（DOR） | All time in the study | It refers to the time from the first assessment of a tumor as CR or PR to the second assessment as PD (Progressive Disease) or death from any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory study endpoint | 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. | Exploring the therapeutic response of subjects with different genotypes to Pola+ZR-CHP regimen using Next-generation sequencing(NGS). |
Countries
China
Outcome results
None listed