AI-Driven Treatment Strategy vs Pola-R-CHP in Untreated LBCL

NCT07594899 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: GUIDANCE-10
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

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.

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 visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )

• Objective response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )

• 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)

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP

EXPERIMENTAL

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; Drug: rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Zanubrutinib; Drug: Lenalidomide; Drug: Decitabine; Drug: Glofitamab

Pola-R-CHP

ACTIVE COMPARATOR

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; Drug: rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Interventions

Polatuzumab Vedotin DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Pola-R-CHP

rituximab DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Pola-R-CHP

Cyclophosphamide DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Pola-R-CHP

Doxorubicin DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Pola-R-CHP

Prednisone DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP; Pola-R-CHP

Zanubrutinib DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP

Lenalidomide DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP

Decitabine DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP

Glofitamab DRUG

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

Genotype-guided targeted agents or glofitamab in combination with Pola-R-CHP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200020, China

Location

MeSH Terms

Interventions

polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; zanubrutinib; Lenalidomide; Decitabine; glofitamab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Weili Zhao

CONTACT

+862164370045 Ext. 610707; zwl_trial@163.com

Pengpeng Xu

CONTACT

+862164370045 Ext. 610707; pengpeng_xu@126.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: May 5, 2026
• First Posted: May 19, 2026
• Study Start: May 6, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)