Diffuse Large B-Cell LymphomaHyDEFNCT06898905
Hyperfractionated Dual Equivalent Fractionated Radiation Therapy
A study testing Bridging Radiation Therapy in people with Diffuse Large B-Cell Lymphoma, run by Yale University at 1 site in United States.
Trial summary
This study evaluates the feasibility and safety of bridging radiation therapy, including a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) undergoing T-cell redirection… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Bridging Radiation Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2025to Apr 2027
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Adult aged 18 years or older.
- Histologically confirmed diagnosis of R/R DLBCL with plan for CAR T or BsAb therapy at Yale New Haven Hospital.
- ECOG performance status 0 to 3.
- Ability to present for once or twice daily (M-F) fractionated radiation therapy, without contraindications for radiotherapy as determined by the treating radiation oncologist.
- Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at time of radiation treatment planning, per standard of care and departmental standard operating procedure. Participants must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
Who cannot join
- Participants who meet any of the following criteria will be disqualified from entering the study:
- Participants who are pregnant or currently breastfeeding.
- Females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential.
- Participants with history of prior radiation exposure for research purposes within the past year, such that participation in this study would place them over the FDA limits for annual radiation exposure.
- Participants who are unable to safely receive FDG PET tracer.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study and attending required study visits (if outpatient); pose a significant risk to the participant; or interfere with interpretation of study data.
- Participants who would not be anticipated to derive any clinical benefit from bridging radiotherapy, are unable to participate in twice daily radiotherapy, or have clinical contraindications to radiation therapy per treating investigator.
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, 1 recruiting
- Recruiting
Yale University
New Haven, Connecticut, 06510
Patricia Brand, 203-785-4095, patricia.brand@yale.edu
Timothy Robinson, MD PhD
About this study
Official title: Hyperfractionated Dual Equivalent Fractionated (HyDEF) Bridging Radiation Therapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Undergoing T-Cell Redirection Therapy
This study evaluates the feasibility and safety of bridging radiation therapy, including a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) undergoing T-cell redirection therapies (CAR T-cell therapy or bispecific antibodies).
Read the detailed description
The purpose of this study is to assess the feasibility and safety of bridging radiation, including a novel method to study the relative effectiveness of hypo- vs. hyperfractionated therapy (i.e., once daily vs. twice daily treatment) in patients with R/R DLBCL undergoing T-cell redirection therapies. This trial will serve as proof-of-concept, feasibility, and safety for a novel dual fractionation trial design, treating the same tumor with two fractionation schedules, paving the way for future radiotherapy trial designs and direct comparison of the efficacy of once vs. twice daily treatment. Correlative studies of immune exhaustion will evaluate the mechanistic underpinnings between radiotherapy and the immune environment. Finally, with the use of RefleXion BGRT, we will collect PET imaging data to provide the basis for this emerging method for administering bridging radiation in lymphoma.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Bridging Radiation Therapy
- Keywords
- HyDEF, bridging radiation, once vs twice daily radiation, bulky disease lymphoma
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bridging Radiation TherapyOther
Study seeks to compare the hypofractionated radiation therapy with hyperfractionated treatment within the same tumor. Each participant will be serving as their own control; half their tumor will receive once daily hypofractionated (QD) bridging radiotherapy, and the other half of their tumor will receive twice daily hyperfractionated (BID) bridging radiotherapy. Either schedule is considered standard of care and this study aims to determine which schedule may prove superior between the two standards.
| Study group | Role | What they receive |
|---|---|---|
| Dual Hyperfractionated Radiation Therapy | Experimental | All patients enrolled will receive radiation as a bridge to subsequent planned T Cell Directed therapy. The same tumor will be treated daily, with one area receiving once daily and the other receiving twice daily radiation therapy. Receives: Other: Bridging Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility Assessment of Bridging Radiation Therapy
Feasibility will be assessed by the proportion of enrolled participants who are successfully treated according to the proposed bridging radiation therapy schema.
Measured: Approximately one year
Safety analysis of Bridging Radiation Therapy
Safety will be assessed by analyzing the incidence of severe (grade ≥ 3) acute toxicities. The therapy will be considered safe if fewer than 30% of study participants receiving dual fractionated radiation therapy experience these toxicities.
Measured: Throughout the study, approximately two years
Dynamics of Circulating Tumor DNA (ctDNA) as a Marker of Minimal Residual Disease
Changes in serum ctDNA levels will be measured at baseline and after radiation therapy (RT) to characterize ctDNA dynamics and assess minimal residual disease. Comparisons will focus on quantitative shifts in ctDNA burden in relation to treatment response.
Measured: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy)
Biomarkers of Hypoxia and Immune Exhaustion in Relation to Treatment Response
Serum biomarkers associated with tumor hypoxia and immune exhaustion will be evaluated at baseline and after radiation therapy (RT). Changes in these biomarkers will be compared to characterize biological responses to treatment and their relationship to clinical outcomes.
Measured: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2025
- Study start30 Oct 2025
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (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.
- More trials run by Yale UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Responsible party
- Sponsor
- Investigators
- Timothy J Robinson, MD PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06898905
- Sponsor's protocol ID
- 2000038092
- Other IDs
- IRG-21-132-60-IRG
- Acronym
- HyDEF
- Status last verified
- Jun 2026
- First submitted
- 18 Mar 2025
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperfractionated Dual Equivalent Fractionated (HyDEF) Bridging Radiation Therapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Undergoing T-Cell Redirection Therapy
- ClinicalTrials.gov ID
- NCT06898905
- Acronym / sponsor ID
- HyDEF / 2000038092
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- HyDEF, bridging radiation, once vs twice daily radiation, bulky disease lymphoma
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Study start
- 30 Oct 2025 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 27 Mar 2025 (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 study evaluates the feasibility and safety of bridging radiation therapy, including a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) undergoing T-cell redirection therapies (CAR T-cell therapy or bispecific antibodies).
Detailed description
The purpose of this study is to assess the feasibility and safety of bridging radiation, including a novel method to study the relative effectiveness of hypo- vs. hyperfractionated therapy (i.e., once daily vs. twice daily treatment) in patients with R/R DLBCL undergoing T-cell redirection therapies. This trial will serve as proof-of-concept, feasibility, and safety for a novel dual fractionation trial design, treating the same tumor with two fractionation schedules, paving the way for future radiotherapy trial designs and direct comparison of the efficacy of once vs. twice daily treatment. Correlative studies of immune exhaustion will evaluate the mechanistic underpinnings between radiotherapy and the immune environment. Finally, with the use of RefleXion BGRT, we will collect PET imaging data to provide the basis for this emerging method for administering bridging radiation in lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dual Hyperfractionated Radiation Therapy | Experimental | Other: Bridging Radiation TherapyAll patients enrolled will receive radiation as a bridge to subsequent planned T Cell Directed therapy. The same tumor will be treated daily, with one area receiving once daily and the other receiving twice daily radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Adult aged 18 years or older.
- Histologically confirmed diagnosis of R/R DLBCL with plan for CAR T or BsAb therapy at Yale New Haven Hospital.
- ECOG performance status 0 to 3.
Key exclusion criteria (7 listed)
- Participants who meet any of the following criteria will be disqualified from entering the study:
- Participants who are pregnant or currently breastfeeding.
- Participants with history of prior radiation exposure for research purposes within the past year, such that participation in this study would place them over the FDA limits for annual radiation exposure.
- Participants who are unable to safely receive FDG PET tracer.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study and attending required study visits (if outpatient); pose a significant risk to the participant; or interfere with interpretation of study data.
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 TherapyStudy seeks to compare the hypofractionated radiation therapy with hyperfractionated treatment within the same tumor. Each participant will be serving as their own control; half their tumor will receive once daily hypofractionated (QD) bridging radiotherapy, and the other half of their tumor will receive twice daily hyperfractionated (BID) bridging radiotherapy. Either schedule is considered standard of care and this study aims to determine which schedule may prove superior between the two standards. | Other | Dual Hyperfractionated Radiation Therapy |
Primary outcome
Feasibility Assessment of Bridging Radiation Therapy
Time frame: Approximately one year
Feasibility will be assessed by the proportion of enrolled participants who are successfully treated according to the proposed bridging radiation therapy schema.
Safety analysis of Bridging Radiation Therapy
Time frame: Throughout the study, approximately two years
Safety will be assessed by analyzing the incidence of severe (grade ≥ 3) acute toxicities. The therapy will be considered safe if fewer than 30% of study participants receiving dual fractionated radiation therapy experience these toxicities.
Dynamics of Circulating Tumor DNA (ctDNA) as a Marker of Minimal Residual Disease
Time frame: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy)
Changes in serum ctDNA levels will be measured at baseline and after radiation therapy (RT) to characterize ctDNA dynamics and assess minimal residual disease. Comparisons will focus on quantitative shifts in ctDNA burden in relation to treatment response.
Biomarkers of Hypoxia and Immune Exhaustion in Relation to Treatment Response
Time frame: Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy).
Serum biomarkers associated with tumor hypoxia and immune exhaustion will be evaluated at baseline and after radiation therapy (RT). Changes in these biomarkers will be compared to characterize biological responses to treatment and their relationship to clinical outcomes.
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 22 Jun 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.
Timothy J Robinson, MD PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bridging Radiation Therapy in people with Diffuse Large B-Cell Lymphoma, run by Yale University 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 7 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 22 Jun 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.
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 Stephanie Ladd (203-785-5702, ycciprojectmanagement@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility Assessment of Bridging Radiation Therapy (time frame: Approximately one year). The study lists 4 primary outcomes in all. 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 22 Jun 2026.