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

NCT07717177 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PRAISE
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

Large B-Cell Lymphoma (LBCL)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Event-free survival

  Up to approximately 24 months

• Complete response rate

  End of treatment completion , an average of 6 months

• Objective response rate

  End of treatment completion , an average of 6 months

• Overall survival

  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.

Study Arms (2)

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen

EXPERIMENTAL

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; Drug: Rituximab (R); Drug: Zanubrutinib; Drug: Lenalidomide; Drug: Glofitamab

ZR2

ACTIVE COMPARATOR

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: Rituximab (R); Drug: Zanubrutinib; Drug: Lenalidomide

Interventions

Rituximab (R) DRUG

Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen; ZR2

Zanubrutinib DRUG

Zanubrutinib PO will be administered as per the schedule specified in the respective arm.

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen; ZR2

Lenalidomide DRUG

Lenalidomide PO will be administered as per the schedule specified in the respective arm.

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen; ZR2

Glofitamab DRUG

Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen

Polatuzumab Vedotin DRUG

Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.

Polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, 200020, China

Location

MeSH Terms

Interventions

polatuzumab vedotin; Rituximab; zanubrutinib; Lenalidomide; glofitamab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Weili Zhao

CONTACT

+862164370045 Ext. 610707; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Shanghai Institute of Hematology

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: July 21, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)