Large B-Cell Lymphoma (LBCL)
Conditions
Brief summary
This is a prospective, open-label, multicenter, randomized controlled study in participants with previously untreated large B-cell lymphoma. 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 Pola-R-CHP. In the experimental arm, participants will receive either genotype-guided targeted agents in combination with Pola-R-CHP or Pola-R-CHP combined with glofitamab, according to their AI-defined risk group and molecular features. Participants in the control arm will receive Pola-R-CHP. The study will evaluate the efficacy and safety of the AI-guided treatment strategy compared with Pola-R-CHP.
Interventions
DRUGPolatuzumab Vedotin
Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
DRUGrituximab
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
DRUGCyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
DRUGDoxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
DRUGPrednisone
Prednisone PO 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.
DRUGDecitabine
Decitabine IV infusion 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
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years with comprehensive geriatric assessment stratified as fit * Previously untreated participants with CD20-positive LBCL (without central nervous system involvement) * ECOG Performance Status of 0, 1, or 2 * After 1 cycle of Pola-R-CHP, classified as intermediate-risk or high-risk by AI-based multimodal stratification * Life expectancy ≥ 3 months * 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) * 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
* Prior solid organ transplantation or SCT * Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina * History or presence of an abnormal ECG that is clinically significant in the investigator's opinion * Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma): * Absolute neutrophil count \<1.0 × 10⁹/L. * Platelet count \<75 × 10⁹/L * Serum AST and ALT ≥ 2.5 x ULN * Total bilirubin ≥ 1.5 x ULN * Serum creatinine clearance \< 30 mL/min (using Cockcroft-Gault formula) * Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety * Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology)：Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HbsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing every month and appropriate antiviral therapy as indicated * Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)：Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA * Participants with a history of progressive multifocal leukoencephalopathy * Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 months after final dose of treatment * Participants with uncontrolled coagulation disorders, connective tissue diseases, severe infectious diseases * Other concurrent and uncontrolled medical conditions that, in the opinion of the investigator, would affect the patient's participation in 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 visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] ) | 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 visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] ) | 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 and 4 (Cycle length=21 days); 30 days after treatment completion | — |
| Patient reported outcome assessed by EORTC QLQ-ELD14 | Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion | — |
| Patient reported outcome assessed by FACT-Lym LymS | Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion | — |
Countries
China
Contacts
CONTACTWeili Zhao
CONTACTPengpeng Xu
Outcome results
None listed