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

NCT07517705 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MRD XRT
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Minimal Residual Disease; ctDNA; PET-CT; MRD-guided therapy; Low-Dose Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• 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).

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

Secondary Outcomes (5)

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

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

• Progression-Free Survival (PFS)

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

• Overall Survival (OS)

  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

  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)

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

Study Arms (2)

Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration

EXPERIMENTAL

Patients with detectable circulating tumor DNA minimal residual disease (ctDNA MRD) after cycle 2 of frontline chemoimmunotherapy and residual PET-avid disease may receive low-dose radiation therapy (LDRT) to PET-positive sites in addition to standard systemic therapy.

Radiation: Low-Dose Radiation Therapy (LDRT); Other: Standard Frontline Chemoimmunotherapy

Arm- B: MRD-Undetectable Standard Therapy

ACTIVE COMPARATOR

Patients with undetectable ctDNA MRD after cycle 2 of frontline chemoimmunotherapy continue standard systemic therapy without the addition of radiation therapy.

Other: Standard Frontline Chemoimmunotherapy

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.

Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration

Standard Frontline Chemoimmunotherapy OTHER

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.

Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration; Arm- B: MRD-Undetectable Standard Therapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

Fred & Pamela Buffet Cancer Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Neoplasm, Residual

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Snegha Ananth, MBBS

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Krishna vamsi Gottipati, MS

CONTACT

(402) 5593518; krgottipati@unmc.edu

IIT Office Clinical Trails Office

CONTACT

(402) 5590963; IITOFFICE@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants receive standard frontline chemoimmunotherapy for diffuse large B-cell lymphoma. Interim PET imaging and circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) testing after cycle 2 guide treatment decisions. Patients with detectable MRD may receive low-dose radiation therapy (LDRT) to residual PET-avid disease sites, while patients with undetectable MRD continue standard therapy without radiation.

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: April 8, 2026
• Study Start: June 12, 2026
• Primary Completion (Estimated): November 12, 2030
• Study Completion (Estimated): November 12, 2032
• Last Updated: May 13, 2026

Record last verified: 2026-03

Locations

US (1)