Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Brief summary
This is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes. After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance. Efficacy and safety assessments will be performed per protocol. Tumor response will be assessed by site investigators according to the 2014 Lugano criteria, including determination of response status, date of response, and date of progression/relapse.
Interventions
DRUGPOLA-R-CHP+Zanubrutinib
Previously untreated DLBCL patients harboring MCD/BN2/N1 subtypes were treated with Pola-ZRCHP (Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone，6 cycles, 21-day cycles), with Rituximab administered for 8 cycles. The regimen consisted of Polatuzumab vedotin (1.8 mg/kg IV, D1), Zanubrutinib (160 mg PO BID), and standard CHP (C 750 mg/m², H 50 mg/m² IV D1; P 100 mg PO D1-5). Following induction, patients achieving ≥Stable Disease (SD) per PET-CT entered the maintenance phase with Zanubrutinib (160 mg PO BID) and Tislelizumab (200 mg IV Q3W, up to 1 year), continuing until progression or unacceptable toxicity. Non-responders (\<SD) discontinued.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of signing informed consent. Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) with MCD/BN2/N1 molecular subtypes defined by LymphGen classification. Previously untreated (treatment-naïve). International Prognostic Index (IPI) score of 2-5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy ≥6 months. At least one measurable lesion in two dimensions, defined as a maximum diameter \>1.5 cm by CT or MRI. Left Ventricular Ejection Fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO). Adequate hematologic function (unless due to underlying disease, e.g., extensive bone marrow involvement, or splenomegaly secondary to splenic involvement deemed by the investigator to be caused by DLBCL; blood product transfusions are allowed), defined as follows: Hemoglobin ≥9.0 g/dL within 7 days prior to first treatment, without packed RBC transfusion. Absolute Neutrophil Count (ANC) ≥1.0 × 10⁹/L. Platelet count ≥75 × 10⁹/L. Female participants of childbearing potential: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate ova. Male participants: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate sperm.
Exclusion criteria
Contraindication to any component of the Pola-ZRCHP regimen. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding onychomycosis) at screening, or any major infection occurring within 4 weeks prior to the first dose of study treatment (as judged by the investigator). Suspected or latent tuberculosis (confirmed by positive IFNγ release assay). Currently pregnant or breastfeeding, or planning a pregnancy during the study period or within 12 months after the last dose. History of confirmed Progressive Multifocal Leukoencephalopathy (PML). Current or history of Central Nervous System (CNS) lymphoma. Evidence of significant, uncontrolled concomitant disease that may affect compliance with the protocol or interpretation of results. Severe or extensive cardiovascular disease, such as New York Heart Association (NYHA) Class III or IV, or objective assessment of Class C or D cardiac disease; myocardial infarction within the past 6 months; unstable arrhythmias; or unstable angina. Clinically significant liver disease, including active viral hepatitis or other hepatitis, current alcohol abuse, or cirrhosis. Any of the following abnormal laboratory values (unless these abnormalities are solely attributable to underlying lymphoma): INR or PT \>1.5 × Upper Limit of Normal (ULN) in the absence of therapeutic anticoagulation. PTT or aPTT \>1.5 × ULN in the absence of lupus anticoagulant. Serum AST and ALT ≥2.5 × ULN. Total bilirubin ≥1.5 × ULN. Estimated creatinine clearance \<40 mL/min (using the Cockcroft-Gault formula). Positive HBV DNA test result. Positive Hepatitis C test result (Hepatitis C virus \[HCV\] antibody serology). Note:Patients with positive HCV antibody are eligible only if the PCR test for HCV RNA is negative. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Event-Free Survival rate（EFS） | Up to 2 years after start of treatment. | The duration from the start of treatment to the first occurrence of disease progression (per the 2014 Lugano Classification), relapse, initiation of new anti-lymphoma therapy, or death from any cause. EFS will be estimated using the Kaplan-Meier method, and between-arm comparisons will be conducted via the log-rank test. Participants who have not experienced any of these events by the end of follow-up will be censored at their last documented disease-evaluation date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days) | The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data. |
| Objective response rate (ORR) | Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 21 days) | The proportion of evaluable participants who achieve objective response (defined as complete response \[CR\] or partial response \[PR\]) following 6 cycles of induction therapy. Response assessment adheres to the 2014 Lugano Classification for Lymphoma: PR requires a ≥50% reduction in the sum of the longest diameters of measurable lesions, with no new lesions or progression of existing non-measurable disease. The analysis population includes participants who complete at least 4 induction cycles and have available post-treatment efficacy evaluation data. |
| 2-Year Overall Survival (OS) | Up to 2 years after start treatment | The duration from randomization to death from any cause. OS will be estimated using the Kaplan-Meier method, with between-arm comparisons performed using the log-rank test. Participants who remain alive at the 2-year follow-up endpoint will be censored at their last confirmed survival date. |
| Incidence of Treatment-Related Adverse Events (TRAE) | From the first dose of study intervention to 30 days after the last dose of study intervention | The proportion of participants experiencing any treatment-related adverse event, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. This includes the incidence of grade 3-4 TRAEs and serious adverse events (SAEs; defined as events that are life-threatening, require hospitalization, result in persistent disability, or are fatal). |
Countries
China
Contacts
CONTACTJinhua Liang, MD
CONTACTWei Xu, PhD
PRINCIPAL_INVESTIGATORWei Xu, PHD
Hematological Department, Jiangsu Province Hospital
Outcome results
None listed