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

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)

Overview

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.

Interventions

• Drug Polatuzumab Vedotin
  Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Rituximab (R)
  Rituximab 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 Lenalidomide
  Lenalidomide 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.

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 completion , an average of 6 months]
• Objective response rate [Time frame: End of treatment completion , an average of 6 months]
• 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, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days]
• Patient reported outcome assessed by EORTC QLQ-ELD14 [Time frame: Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days]
• Patient reported outcome assessed by FACT-Lym LymS [Time frame: Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days]

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

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

Identifiers

NCT: NCT07717177 · PRAISE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗