MRD-Adapted Low-Dose Radiation Therapy During Frontline Chemoimmunotherapy for Diffuse Large B-Cell Lymphoma

Официальное название

Feasibility of MRD-Adapted Mid-Cycle Low-Dose Radiation Combined With Frontline R-Chemoimmunotherapy in Diffuse Large B-Cell Lymphoma (MRD XRT)

Обзор

This prospective feasibility study evaluates a minimal residual disease (MRD)-adapted treatment strategy in patients with diffuse large B-cell lymphoma (DLBCL) receiving frontline chemoimmunotherapy. Circulating tumor DNA (ctDNA)-based MRD testing and interim positron emission tomography (PET) imaging after two cycles of therapy are used to guide treatment decisions. Patients with detectable MRD may receive low-dose radiation therapy (LDRT) to residual PET-avid disease sites in addition to standard systemic therapy, while patients with undetectable MRD continue standard frontline chemoimmunotherapy. The study aims to assess the feasibility and safety of integrating MRD-guided radiation therapy into frontline treatment of DLBCL.

Подробное описание

Diffuse large B-cell lymphoma (DLBCL) is commonly treated with frontline chemoimmunotherapy regimens such as R-CHOP or related combinations. Early response assessment using positron emission tomography (PET) imaging provides prognostic information but may not fully capture minimal residual disease. Circulating tumor DNA (ctDNA)-based MRD assays allow for sensitive detection of molecular residual disease during treatment.

This study evaluates an MRD-adapted treatment strategy that integrates interim PET imaging and ctDNA MRD testing during frontline therapy for DLBCL. Patients receiving standard-of-care chemoimmunotherapy undergo MRD testing and PET imaging after cycle 2 of treatment. Patients with detectable MRD may receive low-dose radiation therapy (LDRT) directed at residual PET-avid disease sites, while patients with undetectable MRD continue standard therapy without radiation.

Вмешательства

• Лучевая терапия Low-Dose Radiation Therapy (LDRT)
  Low-dose radiation therapy delivered to residual PET-avid disease sites identified after interim assessment with PET imaging and MRD testing.
• Другое Standard Frontline Chemoimmunotherapy
  Standard-of-care frontline chemoimmunotherapy regimens for diffuse large B-cell lymphoma, including R-CHOP, Pola-R-CHP, DA-EPOCH-R, R-CEOP, or related regimens as determined by the treating physician.

Первичные конечные точки

• Feasibility of Real-Time MRD-Guided Treatment Strategy [Срок оценки: From initiation of study treatment through completion of frontline therapy (approximately 6 months)]

Вторичные конечные точки (5)

• Overall response rate (ORR), Including Complete Response (CR) and Partial Response (PR) Rates [Срок оценки: From initiation of study treatment through completion of frontline therapy (approximately 6 months)]
• Progression-Free Survival (PFS) [Срок оценки: From initiation of study treatment until disease progression or death, assessed up to 24 months]
• Overall Survival (OS) [Срок оценки: From initiation of study treatment until death from any cause, assessed up to 24 months]
• Impact of Low-Dose Radiation Therapy on Delivery of Systemic Chemoimmunotherapy [Срок оценки: From initiation of study treatment through completion of frontline Chemoimmunotherapy (approximately 6 months)]
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [Срок оценки: From baseline through end of treatment, assessed up to 24 months]

Критерии участия

Критерии включения

• Adults ≥19 years of age
• Biopsy-proven newly diagnosed DLBCL, transformed from indolent lymphoma, Follicular lymphoma grade 3B, post-transplant lymphoproliferative disorder, or any other subtypes of Large B-cell lymphoma under WHO-HAEM5 classification who are eligible and plan to receive 6 cycles of R-chemoimmunotherapy. Note: patients may receive up to one cycle of R-chemoimmunotherapy prior to enrollment.
• Planned to receive 6 cycles of frontline R-chemoimmunotherapy for diseases mentioned in criterion 2
• Presence of measurable disease on imaging, nodal lesion >1.5cm or extra-nodal lesion >1 cm prior to initiation of R-chemoimmunotherapy
• Availability of sufficient and viable baseline FFPE tumor tissue to allow development of a personalized MRD assay

Критерии исключения

• Limited stage (Ann Arbor stage I-II) DLBCL, requiring less than 6 cycles of R-chemoimmunotherapy
• Primary or secondary CNS lymphoma
• Subject has exceeded maximum lifelong cumulative doses of radiation therapy or is unsafe for radiation therapy as determined by the investigator and/or radiation oncologist
• Pregnant and lactating patients
• Has received two or more cycles of R-chemoimmunotherapy relating to this disease

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Fred & Pamela Buffet Cancer Center — Omaha

Идентификаторы

NCT: NCT07517705 · MRD XRT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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