DLBCL - Diffuse Large B Cell LymphomaPhase 1NCT05621096
Low Dose Radiation as Bridging Therapy in Relapsed B-Cell Non-Hodgkin Lymphoma
A Phase 1 study testing Bridging radiation therapy, Liso-cel and Post-infusion radiation in people with DLBCL - Diffuse Large B Cell Lymphoma and High-grade B-cell Lymphoma, run by University of Nebraska at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn about treatment for people with B-cell lymphoma that did not respond to treatment or that has gotten worse after treatment. The aim of this trial is to answer the following questions: If it is realistic to give people radiation treatment before they receive a chimeric… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- DLBCL - Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma
- What is being tested?
- Bridging radiation therapy, Liso-cel and Post-infusion radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2023to Sep 2027
- Phase
- Phase 1
- 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
- Biopsy-proven relapsed or progressive diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, or DLBCL arising from indolent lymphoma meeting an FDA-approved (Food and Drug Administration-approved) indication for liso-cel infusion
- Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist
- Willingness to participate in clinical trial and provide informed consent
- Adequate organ function as assessed by standard institution protocols and United States (US) prescribing information label for comorbidities, heart, and lung function to undergo FDA-approved CAR T-cell therapy as determined by institution
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Age 19 years or older, there is no upper limit to the age
Who cannot join
- Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist
- Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed)
- Requirement for concurrent high dose methotrexate
- Secondary active malignancy that has not been in remission for at least 2 years. This excludes non-melanoma skin cancer, definitively treated stage 1 solid tumor with low risk or recurrence, and curatively treated localized prostate cancer.
- Pregnant or nursing women
- Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as determined by investigator
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- Unwillingness to follow procedures required in the protocol
- Inadequate organ or hematologic conditions that prohibit the use of lymphodepleting chemotherapy
- Use of lymphoma-directed therapy within 14 days of T-cell pheresis
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Feasibility of Low Dose Radiation as Bridging Therapy for Lisocabtagene Maraleucel in Relapsed B-Cell Non-Hodgkin Lymphoma
The goal of this clinical trial is to learn about treatment for people with B-cell lymphoma that did not respond to treatment or that has gotten worse after treatment. The aim of this trial is to answer the following questions:
- If it is realistic to give people radiation treatment before they receive a chimeric antigen receptor (CAR) T-cell treatment for their cancer
- If it is safe to give people radiation treatment before they receive a CAR T-cell treatment for their cancer
Read the detailed description
This is a pilot study to evaluate the feasibility of low-dose radiation therapy in the bridging period between chimeric antigen receptor (CAR) T-cell collection, manufacturing, and infusion (vein-to-vein) in patients with relapsed and refractory aggressive B-cell lymphoma.
Emerging cellular immunotherapies including CAR T-cell therapy have produced remarkable outcomes for this population. The Food and Drug Administration (FDA) has recently approved lisocabtagene maraleucel (liso-cel) for the management of people with relapsed and refractory B-cell lymphoma. Unfortunately, many patients undergoing liso-cel infusion will suffer progression or relapse with devastating consequences. The object of this study is to identify a novel means to enhance liso-cel activity to improve overall outcomes. The investigators hypothesize that the addition of radiation therapy targeting selected sites as bridging therapy prior to lymphodepleting chemotherapy and liso-cel infusion will be effective at improving responses for patients with relapsed and refractory B-cell lymphoma.
Results from this study will provide key justification to expand this therapeutic approach into a larger phase II clinical trial powered to examine the efficacy of this approach.
- Conditions
- DLBCL - Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma, Mediastinal Large B-cell Lymphoma, Indolent B-Cell Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
- Being tested
- Bridging radiation therapy, Liso-cel, Post-infusion radiation
- Medical subject headings
- Dendritic Cell Sarcoma, Interdigitating, Lymphoma, Follicular, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bridging radiation therapyRadiation
Days -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received.
Liso-celBiological
Also called Chimeric antigen receptor (CAR) T-cell product
Day 0: Patients will receive an infusion of liso-cel CAR T-cell product.
Prior to the liso-cell infusion (Days -5 to -3), patients will receive lymphodepleting chemotherapy using fludarabine 30mg/m2 and cyclophosphamide 300mg/m2 per institutional standard procedures.
Post-infusion radiationRadiation
Days 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation. Receives: Radiation: Bridging radiation therapy; Biological: Liso-cel; Radiation: Post-infusion radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of the intervention in the proposed study population
The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (>70% vs <70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy.
Measured: Up to 90 days
Secondary outcomes (8)
Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention
Assessed via the incidence of combined Grade 3 and 4 cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) events as measured by the American Society of Transplant and Cellular Therapy (ASTCT) consensus grading. The grading scale ranges from Grade 1 to 4, with a higher grade indicating a worse outcome. Assessed from the cumulative CRS and ICANS events occurring by the D+30 visit.
Measured: Up to 120 days
Evaluate the response to the study intervention of radiation and CAR T-cell therapy
Response rate will be assessed via PET/CT (positron emission tomography/computed tomography) using Lugano criteria. Overall response rate (ORR) will be defined as the proportion of patients with either a complete response (CR) or a partial response (PR) at D+100. For ORR, CR, and PR: two-sided exact binomial 95% confidence interval of response rate will be constructed to assess the precision of the point estimate.
Measured: Up to 190 days
Evaluate progression-free survival (PFS) following the study intervention
PFS will be measured using the Kaplan-Meier method. Disease progression will be measured according to clinical and imaging assessment (Lugano criteria) and will require biopsy confirmation.
Measured: Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years
Evaluate duration of response (DOR) following CAR T-cell therapy
DOR will be summarized using the Kaplan-Meier method, but only for patients who have achieved a response of at least partial response. DOR is defined by time of first response (D+30 visit) to disease progression, start of new antineoplastic therapy due to efficacy concerns, or death from any cause.
Measured: Up to 2 years
Evaluate overall survival (OS) following study intervention
OS will be analyzed by the Kaplan-Meier method. Subjects alive at last follow up will be censored.
Measured: Up to 2 years
Evaluate the rate of prolonged cytopenias following the intervention
The rate of prolonged cytopenias will be measured as a proportion of subjects with Grade 3 or higher hematologic toxicities per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria at the D+100 visit. The 95% confidence interval will be estimated.
The CTCAE v5.0 grading system ranges from Grade 0 to 5, with a higher grade indicating a worse outcome.
Measured: Up to 190 days
Monitor overall safety and toxicity of the intervention
Toxicity will be graded using CTCAE v5.0 guidelines. Grade 3 or higher toxicities will be tabulated using percentages at each follow up. The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading system ranges from Grade 0 to 5, with a higher grade indicating a worse outcome.
Measured: Up to 270 days
Monitor Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events
Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events will be collected for all grades as measured by American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria.
The ASTCT consensus criteria grading system ranges from Grade 1 to 4, with a higher grade indicating a worse outcome.
Measured: Up to 270 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2022
- Study start21 Mar 2023
- Primary completion20 Jan 2025
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DLBCL - Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Christopher R D'Angelo, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05621096
- Sponsor's protocol ID
- 0770-22-FB
- Status last verified
- Oct 2026
- First submitted
- 27 Oct 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Low Dose Radiation as Bridging Therapy for Lisocabtagene Maraleucel in Relapsed B-Cell Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT05621096
- Acronym / sponsor ID
- 0770-22-FB
- Conditions
- DLBCL - Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma, Mediastinal Large B-cell Lymphoma, Indolent B-Cell Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 21 Mar 2023 (actual)
- Primary completion
- 20 Jan 2025 (actual)
- Study completion
- Sep 2027 (estimated)
- First posted
- 17 Nov 2022 (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.
The goal of this clinical trial is to learn about treatment for people with B-cell lymphoma that did not respond to treatment or that has gotten worse after treatment. The aim of this trial is to answer the following questions:
- If it is realistic to give people radiation treatment before they receive a chimeric antigen receptor (CAR) T-cell treatment for their cancer
- If it is safe to give people radiation treatment before they receive a CAR T-cell treatment for their cancer
Detailed description
This is a pilot study to evaluate the feasibility of low-dose radiation therapy in the bridging period between chimeric antigen receptor (CAR) T-cell collection, manufacturing, and infusion (vein-to-vein) in patients with relapsed and refractory aggressive B-cell lymphoma.
Emerging cellular immunotherapies including CAR T-cell therapy have produced remarkable outcomes for this population. The Food and Drug Administration (FDA) has recently approved lisocabtagene maraleucel (liso-cel) for the management of people with relapsed and refractory B-cell lymphoma. Unfortunately, many patients undergoing liso-cel infusion will suffer progression or relapse with devastating consequences. The object of this study is to identify a novel means to enhance liso-cel activity to improve overall outcomes. The investigators hypothesize that the addition of radiation therapy targeting selected sites as bridging therapy prior to lymphodepleting chemotherapy and liso-cel infusion will be effective at improving responses for patients with relapsed and refractory B-cell lymphoma.
Results from this study will provide key justification to expand this therapeutic approach into a larger phase II clinical trial powered to examine the efficacy of this approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Radiation: Bridging radiation therapy, Biological: Liso-cel, Radiation: Post-infusion radiationSubjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Biopsy-proven relapsed or progressive diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, or DLBCL arising from indolent lymphoma meeting an FDA-approved (Food and Drug Administration-approved) indication for liso-cel infusion
- Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist
- Willingness to participate in clinical trial and provide informed consent
- Adequate organ function as assessed by standard institution protocols and United States (US) prescribing information label for comorbidities, heart, and lung function to undergo FDA-approved CAR T-cell therapy as determined by institution
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Key exclusion criteria (9 listed)
- Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist
- Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed)
- Requirement for concurrent high dose methotrexate
- Secondary active malignancy that has not been in remission for at least 2 years. This excludes non-melanoma skin cancer, definitively treated stage 1 solid tumor with low risk or recurrence, and curatively treated localized prostate cancer.
- Pregnant or nursing women
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 |
|---|---|---|
| Bridging radiation therapyDays -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received. | Radiation | Single arm |
| Liso-celAlso: Chimeric antigen receptor (CAR) T-cell productDay 0: Patients will receive an infusion of liso-cel CAR T-cell product. Prior to the liso-cell infusion (Days -5 to -3), patients will receive lymphodepleting chemotherapy using fludarabine 30mg/m2 and cyclophosphamide 300mg/m2 per institutional standard procedures. | Biological | Single arm |
| Post-infusion radiationDays 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy. | Radiation | Single arm |
Primary outcome
Feasibility of the intervention in the proposed study population
Time frame: Up to 90 days
The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (>70% vs <70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy.
8 secondary outcomes
Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention
Time frame: Up to 120 days
Evaluate the response to the study intervention of radiation and CAR T-cell therapy
Time frame: Up to 190 days
Evaluate progression-free survival (PFS) following the study intervention
Time frame: Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years
Evaluate duration of response (DOR) following CAR T-cell therapy
Time frame: Up to 2 years
Evaluate overall survival (OS) following study intervention
Time frame: Up to 2 years
Evaluate the rate of prolonged cytopenias following the intervention
Time frame: Up to 190 days
Monitor overall safety and toxicity of the intervention
Time frame: Up to 270 days
Monitor Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events
Time frame: Up to 270 days
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 8 Oct 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Christopher R D'Angelo, MD 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 1 study testing Bridging radiation therapy, Liso-cel and Post-infusion radiation in people with DLBCL - Diffuse Large B Cell Lymphoma and High-grade 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 6 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 8 Oct 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of the intervention in the proposed study population (time frame: Up to 90 days). 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 8 Oct 2026; AzTrials last refreshed its copy on 3 Nov 2026.