Large B-Cell Lymphoma (LBCL)
Conditions
Brief summary
This is a prospective, open-label, multicenter, randomized controlled study in older treatment-naive patients with LBCL. Participants will be stratified into different risk groups using an AI-based multimodal model. Those classified as intermediate- or high-risk will be randomized in a 1:1 ratio to receive either an AI-guided treatment strategy or ZR2. In the experimental arm, participants will receive polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen (polatuzumab vedotin, zanubrutinib, lenalidomide, and glofitamab), according to their AI-defined risk group. Participants in the control arm will receive ZR2. The study will evaluate the efficacy and safety of the AI-guided treatment strategy compared with ZR2.
Interventions
DRUGPolatuzumab Vedotin
Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
DRUGRituximab (R)
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
DRUGZanubrutinib
Zanubrutinib PO will be administered as per the schedule specified in the respective arm.
DRUGLenalidomide
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
DRUGGlofitamab
Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. * After 1 cycle of ZR2, classified as intermediate-risk or high-risk by AI-based multimodal stratification * 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 | Description |
|---|---|---|
| Progression-free survival | From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months) | PFS, defined as the time from randomization to the first occurrence of disease progression or relapse using the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | Up to approximately 24 months | EFS, defined as the time from date of randomization to the earliest occurrence of any of the following: Disease progression/relapse; Death due to any cause; The primary efficacy reason that leads to initiation of NALT (other than disease progression/relapse). If biopsy is obtained after treatment completion and is positive for residual disease regardless of whether NALT is initiated or not. |
| Complete response rate | End of treatment completion , an average of 6 months | CR rate at the end of treatment by FDG-PET defined as the proportion of participants with CR at the end of treatment according to the 2014 Lugano Response Criteria |
| Objective response rate | End of treatment completion , an average of 6 months | ORR at treatment completion or discontinuation defined as the proportion of participants with partial response (PR) or CR at the end of treatment according to the 2014 Lugano Response Criteria |
| Overall survival | Up to approximately 3 years | OS defined as the time from randomization to death from any cause |
| Duration of response | From documentation of CR/PR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 3 years. | — |
| Duration of complete response | From documentation of CR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 3 years. | — |
| 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 assessed by EORTC QLQ-C30 (Verison 3.0) | Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days | Patient-reported outcome will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Version 3.0 (EORTC QLQ-C30). Scores are linearly transformed to a scale from 0 to 100. For the global health status/quality of life and functional scales, higher scores indicate better health status, quality of life, or functioning. For symptom scales or symptom items, higher scores indicate greater symptom burden or worse symptoms. |
| Patient reported outcome assessed by EORTC QLQ-ELD14 | Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days | Patient-reported outcome will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Elderly 14 (EORTC QLQ-ELD14). Scores are linearly transformed to a scale from 0 to 100. Higher scores indicate a higher level of the construct being measured. For functioning or support-related scales, higher scores indicate better functioning or greater support. For symptom, worry, or burden-related scales, higher scores indicate greater symptom burden, worry, or worse outcome. |
| Patient reported outcome assessed by FACT-Lym LymS | Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days | Patient-reported outcome will be assessed using the Functional Assessment of Cancer Therapy-Lymphoma lymphoma-specific subscale (FACT-Lym LymS). The FACT-Lym LymS score ranges from 0 to 60, with higher scores indicating better lymphoma-specific quality of life and fewer lymphoma-related symptoms. |
Countries
China
Contacts
CONTACTWeili Zhao
Outcome results
None listed