Hyperfractionated Dual Equivalent Fractionated Radiation Therapy

NCT ID: NCT06898905

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-30
• Study Completion Date: 2027-04-30

Brief Summary

This study evaluates the feasibility and safety of 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 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, investigators 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bridging Radiation Therapy

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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 tumor size greater than or equal to 5 cm in its greatest dimension 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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Cancer Society, Inc.

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy J Robinson, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stephanie Ladd

Role: CONTACT

ycciprojectmanagement@yale.edu

203-785-5702

Facility Contacts

Patricia Brand

Role: primary

patricia.brand@yale.edu

203-785-4095

Other Identifiers

IRG-21-132-60-IRG

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2000038092

Identifier Type: -

Identifier Source: org_study_id