AI-Driven Treatment Strategy vs ZR2 in Older Treatment-naive Patients With LBCL (PRAISE)

A Study to Evaluate the Efficacy and Safety of an AI-Driven Treatment Strategy Versus ZR2 in Older Treatment-naive Patients With Large B-cell Lymphoma (LBCL)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Large B-Cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: Polatuzumab Vedotin; Drug: Lenalidomide; Drug: Zanubrutinib; Drug: Glofitamab; Drug: Rituximab (R)

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: +862164370045 Ext. 610707; Email: zwl_trial@163.com

Study Locations

• China
  • Shanghai, China, 200020
    • Ruijin Hospital
    • Contact: Weili Zhao; Phone Number: 64370045; Email: zwl_trial@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen; Participants will receive zanubrutinib 160 mg BID orally (PO) on Days 1-21, lenalidomide 25 mg/day PO on Days 2-11, and rituximab 375 mg/m² intravenously (IV) on Day 1 of the first cycle. For the remaining five cycles, participants will receive either Pola-ZR2 or Pola-ZR-Glo. In the Pola-ZR2 regimen, participants will receive ZR2 in combination with polatuzumab vedotin 1.8 mg/kg IV on Cycle 2 Day 2 and on Day 1 of Cycles 3-6. In the Pola-ZR-Glo regimen, participants will receive zanubrutinib 160 mg BID PO on Days 1-21 of Cycles 1-6, lenalidomide 25 mg/day orally on Days 2-11 of Cycles 1-6, polatuzumab vedotin 1.8 mg/kg intravenously on Cycle 2 Day 2 and on Day 1 of Cycles 3-6, and glofitamab intravenously with step-up dosing of 2.5 mg on Cycle 2 Day 8, 10 mg on Cycle 2 Day 15, and 30 mg on Day 1 of Cycles 3-12. For participants receiving the ZR2 or Pola-ZR2 regimen, lenalidomide maintenance will be continued for 18 weeks after six cycles of treatment. Each treatment cycle is 21 days.	Drug: Polatuzumab Vedotin; Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Lenalidomide; Lenalidomide PO will be administered as per the schedule specified in the respective arm.; Drug: Zanubrutinib; Zanubrutinib PO will be administered as per the schedule specified in the respective arm.; Drug: Glofitamab; Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Rituximab (R); Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
Active Comparator: ZR2; Participants will receive zanubrutinib 160 mg BID orally (PO) on Days 1-21, lenalidomide 25 mg/day orally on Days 2-11, and rituximab 375 mg/m² intravenously (IV) on Day 1 of every 21-day cycle for 6 cycles.	Drug: Lenalidomide; Lenalidomide PO will be administered as per the schedule specified in the respective arm.; Drug: Zanubrutinib; Zanubrutinib PO will be administered as per the schedule specified in the respective arm.; Drug: Rituximab (R); Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	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.	From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0		From enrollment to study completion, a maximum of 4 years
Event-free survival	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.	Up to approximately 24 months
Overall survival	OS defined as the time from randomization to death from any cause	Up to approximately 3 years
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.
Complete response rate	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	End of treatment completion , an average of 6 months
Objective response rate	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	End of treatment completion , an average of 6 months
Patient reported outcome assessed by EORTC QLQ-C30 (Verison 3.0)	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.	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 assessed by EORTC QLQ-ELD14	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.	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 assessed by FACT-Lym LymS	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.	Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: July 18, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Rituximab; zanubrutinib; polatuzumab vedotin; glofitamab
• Other Study ID Numbers: PRAISE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No