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

Official title

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

Overview

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.

Interventions

• Drug Polatuzumab Vedotin
  Polatuzumab vedotin 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.
• 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 Zanubrutinib
  Zanubrutinib 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 Glofitamab
  Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.

Primary outcome measures

• Progression-free survival [Time frame: 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 (10)

• Event-free survival [Time frame: Up to approximately 24 months]
• Complete response rate [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )]
• Objective response rate [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )]
• Overall survival [Time frame: Up to approximately 3 years]
• Duration of response [Time frame: 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 [Time frame: From documentation of CR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 3 years.]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 [Time frame: From enrollment to study completion, a maximum of 4 years]
• Patient reported outcome assessed by EORTC QLQ-C30 (Verison 3.0) [Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]
• Patient reported outcome assessed by EORTC QLQ-ELD14 [Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]
• Patient reported outcome assessed by FACT-Lym LymS [Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07594899 · GUIDANCE-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗