Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Minimal Residual Disease, ctDNA, PET-CT, MRD-guided therapy, Low-Dose Radiation Therapy
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.
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.
Interventions
RADIATIONLow-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.
OTHERStandard 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.
Sponsors
University of Nebraska
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Real-Time MRD-Guided Treatment Strategy | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Proportion of patients achieving complete response (CR) or overall response (CR+PR) based on PET-CT and imaging criteria |
| Progression-Free Survival (PFS) | From initiation of study treatment until disease progression or death, assessed up to 24 months | Time from initiation of frontline therapy until disease progression or death from any cause. will be analyzed using Kaplan-Meier curves |
| Overall Survival (OS) | From initiation of study treatment until death from any cause, assessed up to 24 months | Time from initiation of frontline therapy until death from any cause. will be analyzed using Kaplan-Meier curves |
| Impact of Low-Dose Radiation Therapy on Delivery of Systemic Chemoimmunotherapy | From initiation of study treatment through completion of frontline Chemoimmunotherapy (approximately 6 months) | Assessment of the impact of mid-cycle low dose radiation therapy on the delivery of planned systemic chemoimmunotherapy. |
| 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 | Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire. |
Countries
United States
Contacts
CONTACTKrishna vamsi Gottipati, MS
CONTACTIIT Office Clinical Trails Office
PRINCIPAL_INVESTIGATORSnegha Ananth, MBBS
University of Nebraska
Outcome results
None listed