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

Phase 2Not Yet RecruitingNCT07517705

University of Nebraska50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

Low-Dose Radiation Therapy (LDRT)RADIATION

Low-dose radiation therapy delivered to residual PET-avid disease sites identified after interim assessment with PET imaging and MRD testing.

Standard Frontline ChemoimmunotherapyOTHER

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.

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adults ≥19 years of age 2. 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. 3. Planned to receive 6 cycles of frontline R-chemoimmunotherapy for diseases mentioned in criterion 2 4. Presence of measurable disease on imaging, nodal lesion \>1.5cm or extra-nodal lesion \>1 cm prior to initiation of R-chemoimmunotherapy 5. Availability of sufficient and viable baseline FFPE tumor tissue to allow development of a personalized MRD assay Exclusion Criteria: 1. Limited stage (Ann Arbor stage I-II) DLBCL, requiring less than 6 cycles of R-chemoimmunotherapy 2. Primary or secondary CNS lymphoma 3. 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 4. Pregnant and lactating patients 5. Has received two or more cycles of R-chemoimmunotherapy relating to this disease

Outcomes

Primary Outcomes

Feasibility of Real-Time MRD-Guided Treatment Strategy

The proportion of enrolled patients who successfully complete protocol-specified ctDNA MRD testing after 2 cycles of frontline chemoimmunotherapy. Among patients with detectable MRD after cycle 2, the proportion who successfully receive protocol-defined low-dose radiation therapy (LDRT).

Time frame: From initiation of study treatment through completion of frontline therapy (approximately 6 months)

Secondary Outcomes

Overall response rate (ORR), Including Complete Response (CR) and Partial Response (PR) Rates

Proportion of patients achieving complete response (CR) or overall response (CR+PR) based on PET-CT and imaging criteria

Time frame: From initiation of study treatment through completion of frontline therapy (approximately 6 months)

Progression-Free Survival (PFS)

Time from initiation of frontline therapy until disease progression or death from any cause. will be analyzed using Kaplan-Meier curves

Time frame: From initiation of study treatment until disease progression or death, assessed up to 24 months

Overall Survival (OS)

Time from initiation of frontline therapy until death from any cause. will be analyzed using Kaplan-Meier curves

Time frame: 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

Assessment of the impact of mid-cycle low dose radiation therapy on the delivery of planned systemic chemoimmunotherapy.

Time frame: 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)

Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire.

Time frame: From baseline through end of treatment, assessed up to 24 months