Large B-Cell Lymphoma (LBCL)
Conditions
Keywords
large B-cell lymphoma, polatuzumab vedotin, zanubrutinib, lenalidomide, glofitamab, older patients, unfit, frail
Brief summary
This is a prospective, single-center, open-label, single-arm clinical study designed to evaluate the efficacy and safety of Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen in older treatment-naive patients with large B-cell lymphoma.
Interventions
DRUGPola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen
Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 12 cycles. Dosage: Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of Cycles 2-6 (each Q3W). Zanubrutinib (160mg bid p.o.) will be administered from D1 to D21 through Cycles 1-6 Q3W. Lenalidomide (25mg qd p.o.) will be administered from D2 to D11 through Cycles 1-6 Q3W. Glofitamab will be administered i.v. on a step-up dosing schedule starting on Day 8 of Cycle 1 (2.5 mg), Day 15 of Cycle 1 (10 mg), followed by 30 mg on Day 1 of Cycles 2-12, with each cycle being 21 days. A single dose of obinutuzumab 1000 mg will be administered intravenously on Day 1 of Cycle 1.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must satisfy all of the following criteria to be enrolled in the study: * Histologically-confirmed large B-cell lymphoma (without central nervous system involvement) * Aged ≥ 70 years old with comprehensive geriatric assessment stratified as unfit or frail, or those who decline immunochemotherapy. * Eastern Cooperative Oncology Group Performance Status 0-2 * At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters) * Life expectancy of at least 3 months determined by researchers * The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research. * Anti-lymphoma drugs have not been used before (except glucocorticoids)
Exclusion criteria
Presence of any of the following criteria will exclude a patient from enrollment: * Uncontrolled blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases * Laboratory measures meet the following criteria at screening (unless caused by lymphoma): Neutrophils\<1.0×10\^9/L Platelets\<75×10\^9/L ALT or AST is 2.5 times higher than the upper limits of normal (ULN), serum bilirubin are 1.5 times higher than the ULN. eGFR is lower than 30ml/min/1.73m\^2 (according to Cockcroft-Gault Equation or MDRD Equation). * uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction\<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval\>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block * Patients with HbsAg positive are required to have HBV DNA\<1.0×10\^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA\<1.0×10\^3 IU/ml is required before entering the group * Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol * HIV-infected patients * History of stroke or intracranial hemorrhage within 6 months prior to start of therapy * Other medical conditions determined by the researchers that may affect the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival | Baseline up to data cut-off (up to approximately 2 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | Baseline up to data cut-off (up to approximately 2 years) | — |
| Complete response rate | At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days) | — |
| Objective response rate | At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days) | — |
| Overall Survival | Baseline up to data cut-off (up to approximately 2 years) | — |
| DoR | From documentation of CR/PR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 32 months. | — |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 | From enrollment to study completion, a maximum of 4 years | — |
| Patient reported outcome | Day 1 of Cycles 1, 4 and 7 (Cycle length=21 days); 30 days after treatment completion | Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0), EORTC QLQ-ELD14 and FACT-Lym LymS. |
Countries
China
Contacts
CONTACTWeili Zhao
CONTACTPengpeng Xu
Outcome results
None listed