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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Polatuzumab Vedotin
  Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат rituximab
  Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Cyclophosphamide
  Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Doxorubicin
  Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Prednisone
  Prednisone PO will be administered as per the schedule specified in the respective arm.
• Препарат Zanubrutinib
  Zanubrutinib PO will be administered as per the schedule specified in the respective arm.
• Препарат Lenalidomide
  Lenalidomide PO will be administered as per the schedule specified in the respective arm.
• Препарат Decitabine
  Decitabine IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Glofitamab
  Glofitamab IV infusion will be administered as per the schedule specified in the respective arm.

Первичные конечные точки

• Progression-free survival [Срок оценки: From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)]

Вторичные конечные точки (10)

• Event-free survival [Срок оценки: Up to approximately 24 months]
• Complete response rate [Срок оценки: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )]
• Objective response rate [Срок оценки: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] )]
• Overall survival [Срок оценки: Up to approximately 3 years]
• Duration of response [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From enrollment to study completion, a maximum of 4 years]
• Patient reported outcome assessed by EORTC QLQ-C30 (Verison 3.0) [Срок оценки: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]
• Patient reported outcome assessed by EORTC QLQ-ELD14 [Срок оценки: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]
• Patient reported outcome assessed by FACT-Lym LymS [Срок оценки: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT07594899 · GUIDANCE-10

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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