Diffuse Large B-Cell LymphomaPhase 2NCT07517705
MRD-Adapted Low-Dose Radiation Therapy During Frontline Chemoimmunotherapy for Diffuse Large B-Cell Lymphoma
A Phase 2 study testing Low-Dose Radiation Therapy (LDRT) and Standard Frontline Chemoimmunotherapy in people with Diffuse Large B-Cell Lymphoma, run by University of Nebraska at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Low-Dose Radiation Therapy (LDRT) and Standard Frontline Chemoimmunotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2026to 12 Nov 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Fred & Pamela Buffet Cancer Center
Omaha, Nebraska, 68198
Snegha Ananth, MBBS, (402)559-3848, sananth@unmc.edu
About this study
Official title: Feasibility of MRD-Adapted Mid-Cycle Low-Dose Radiation Combined With Frontline R-Chemoimmunotherapy in Diffuse Large B-Cell Lymphoma (MRD XRT)
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.
Read the detailed description
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.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Low-Dose Radiation Therapy (LDRT), Standard Frontline Chemoimmunotherapy
- Keywords
- Minimal Residual Disease, ctDNA, PET-CT, MRD-guided therapy, Low-Dose Radiation Therapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Standard Frontline Chemoimmunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Proportion of patients achieving complete response (CR) or overall response (CR+PR) based on PET-CT and imaging criteria
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: From baseline through end of treatment, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start12 Jun 2026 (estimated)
- Primary completion12 Nov 2030 (estimated)
- Study completion12 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Snegha Ananth, MBBS, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07517705
- Sponsor's protocol ID
- MRD XRT
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2026
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of MRD-Adapted Mid-Cycle Low-Dose Radiation Combined With Frontline R-Chemoimmunotherapy in Diffuse Large B-Cell Lymphoma (MRD XRT)
- ClinicalTrials.gov ID
- NCT07517705
- Acronym / sponsor ID
- MRD XRT
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- Minimal Residual Disease, ctDNA, PET-CT, MRD-guided therapy, Low-Dose Radiation Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 12 Jun 2026 (estimated)
- Primary completion
- 12 Nov 2030 (estimated)
- Study completion
- 12 Nov 2032 (estimated)
- First posted
- 8 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration | Experimental | Radiation: Low-Dose Radiation Therapy (LDRT), Other: Standard Frontline ChemoimmunotherapyPatients 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. |
| Arm- B: MRD-Undetectable Standard Therapy | Active comparator | Other: Standard Frontline ChemoimmunotherapyPatients with undetectable ctDNA MRD after cycle 2 of frontline chemoimmunotherapy continue standard systemic therapy without the addition of radiation therapy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Radiation | Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration |
| Standard Frontline ChemoimmunotherapyStandard-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. | Other | Arm- A: MRD-Detectable with Protocol-Directed LDRT Consideration, Arm- B: MRD-Undetectable Standard Therapy |
Primary outcome
Feasibility of Real-Time MRD-Guided Treatment Strategy
Time frame: From initiation of study treatment through completion of frontline therapy (approximately 6 months)
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).
5 secondary outcomes
Overall response rate (ORR), Including Complete Response (CR) and Partial Response (PR) Rates
Time frame: From initiation of study treatment through completion of frontline therapy (approximately 6 months)
Progression-Free Survival (PFS)
Time frame: From initiation of study treatment until disease progression or death, assessed up to 24 months
Overall Survival (OS)
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
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)
Time frame: From baseline through end of treatment, assessed up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Snegha Ananth, MBBS principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-Dose Radiation Therapy (LDRT) and Standard Frontline Chemoimmunotherapy in people with Diffuse Large B-Cell Lymphoma, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Krishna vamsi Gottipati, MS ((402) 5593518, krgottipati@unmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of Real-Time MRD-Guided Treatment Strategy (time frame: From initiation of study treatment through completion of frontline therapy (approximately 6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.