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

Официальное название

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)

Обзор

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.

Вмешательства

• Препарат Polatuzumab Vedotin
  Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Rituximab (R)
  Rituximab IV infusion 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 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 completion , an average of 6 months]
• Objective response rate [Срок оценки: End of treatment completion , an average of 6 months]
• 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, 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 [Срок оценки: 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 [Срок оценки: Day 1 of Cycles 1, 4 and 7 (Pola-ZR-Glo regimen only); 30 days after treatment completion. Cycle length=21 days]

Критерии участия

Критерии включения

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)

Критерии исключения

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

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 — Шанхай

Идентификаторы

NCT: NCT07717177 · PRAISE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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