Hyperfractionated Dual Equivalent Fractionated Radiation Therapy (HyDEF)

June 17, 2026 updated by: Yale University

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Timothy Robinson, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Adult aged 18 years or older.
  4. Histologically confirmed diagnosis of R/R DLBCL with plan for CAR T or BsAb therapy at Yale New Haven Hospital.
  5. ECOG performance status 0 to 3.
  6. Ability to present for once or twice daily (M-F) fractionated radiation therapy, without contraindications for radiotherapy as determined by the treating radiation oncologist.
  7. 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.

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

  1. Participants who are pregnant or currently breastfeeding.

    a. Females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential.

  2. 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.
  3. Participants who are unable to safely receive FDG PET tracer.
  4. 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.
  5. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dual Hyperfractionated Radiation Therapy
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.
Other: Bridging Radiation Therapy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Approximately one year
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.
Throughout the study, approximately two years
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.
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
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.
Baseline (0-7 days prior to radiation therapy) to post-radiation therapy (prior to initiation of lymphodepleting chemotherapy).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

American Cancer Society, Inc.

Investigators

  • Principal Investigator: Timothy J Robinson, MD PhD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2025

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

March 18, 2025

First Submitted That Met QC Criteria

March 25, 2025

First Posted (Actual)

March 27, 2025

Study Record Updates

Last Update Posted (Actual)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000038092
  • IRG-21-132-60-IRG (Other Grant/Funding Number: American Cancer Society)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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