AI-Driven Treatment Strategy vs ZR2 in Older Treatment-naive Patients With LBCL | NCT07717177

NCT07717177

Overview

NCT ID: NCT07717177
Lead Sponsor: Ruijin HospitalOTHER
Official Title: 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)
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)

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Jul 21, 2026Actual
Start Date: Jun 30, 2026Estimated
Primary Completion Date: Jun 30, 2029Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: 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

Study Type: Interventional
Phase: Phase 2
Enrollment: 112Estimated
Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Contacts and Locations

Central Contacts: Weili ZhaoContact
zwl_trial@163.com+862164370045 Ext. 610707

Similar Studies

Participant Group/Arms

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

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

ZR2Active 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)