AI-Driven Treatment Strategy vs Pola-R-CHP in Untreated LBCL (GUIDANCE-10)

A Study to Evaluate the Efficacy and Safety of an AI-Driven Treatment Strategy Versus Pola-R-CHP in Patients With Previously Untreated Large B-Cell Lymphoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Large B-Cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Lenalidomide; Drug: Decitabine; Drug: Zanubrutinib; Drug: Glofitamab; Drug: rituximab

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: +862164370045 Ext. 610707; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu; Phone Number: +862164370045 Ext. 610707; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200020
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Weili Zhao; Phone Number: 64370045; Email: zwl_trial@163.com

Participation Criteria

Eligibility Criteria

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

Description

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

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: Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 2, rituximab 375 milligrams per square meter (mg/m²) IV on Day 1, cyclophosphamide 750 mg/m² IV on Day 2, doxorubicin 50 mg/m² IV on Day 2, and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 2-6 of the first 21-day cycle. For the remaining five cycles, participants will receive standard Pola-R-CHP in combination with one of the following: zanubrutinib 160 mg BID PO on Days 1-21, lenalidomide 25 mg/day PO on Days 2-11, decitabine 10 mg/m²/day IV on Days -5 to -1, or glofitamab administered IV 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 8 of Cycles 3-6. 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: Cyclophosphamide; Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Doxorubicin; Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Prednisone; Prednisone PO 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: Decitabine; Decitabine IV infusion 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; Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
Active Comparator: Pola-R-CHP; Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day2, rituximab 375 milligrams per square meter (mg/m²) IV on Day 1, cyclophosphamide 750 mg/m² IV on Day 2, doxorubicin 50 mg/m² IV on Day 2, and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 2-6 of every 21-day cycle for 6 cycles.	Drug: Polatuzumab Vedotin; Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Cyclophosphamide; Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Doxorubicin; Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.; Drug: Prednisone; Prednisone PO will be administered as per the schedule specified in the respective arm.; Drug: rituximab; 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
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 visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )
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 visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )
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.
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

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 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; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Carboxylic Acids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aza Compounds; Nucleosides; Ribonucleosides; Pregnadienediols; Anthracyclines; Naphthacenes; Aminoglycosides; Antibodies, Monoclonal, Murine-Derived; Daunorubicin; Azacitidine; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Decitabine; Lenalidomide; Rituximab; Prednisone; Cyclophosphamide; Doxorubicin; zanubrutinib; polatuzumab vedotin; glofitamab
• Other Study ID Numbers: GUIDANCE-10

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