Radiation Therapy for B-Cell Lymphoma

(HyDEF Trial)

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Pregnancy, Breastfeeding, Prior radiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods of using radiation therapy for individuals with diffuse large B-cell lymphoma, a type of blood cancer that has recurred or is difficult to treat. The study tests whether administering radiation in different patterns (once or twice a day) can better prepare patients for other cancer treatments, such as CAR T-cell therapy. Participants with this cancer type, particularly those with a large tumor (5 cm or more) and who can tolerate frequent radiation sessions, are sought. As an unphased trial, this study provides a unique opportunity to contribute to innovative cancer treatment strategies.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this method is safe for treating B-cell lymphoma?

Research has shown that using a special type of radiation therapy, called hyperfractionated radiation, before CAR T-cell therapy is safe for patients with relapsed or hard-to-treat diffuse large B-cell lymphoma. Previous studies found that patients generally tolerated this radiation treatment well, without severe side effects. Some patients might experience mild reactions, such as skin irritation or tiredness, but these are usually manageable. Overall, this therapy complements the planned CAR T-cell treatments, providing a safe option for trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Hyperfractionated Dual Equivalent Fractionated Radiation Therapy for B-Cell Lymphoma because it offers a novel approach to radiation delivery. Unlike traditional radiation therapy, which typically involves a single daily dose, this method administers radiation to the same tumor twice daily in one area and once daily in another. This intensified schedule aims to effectively control the tumor while potentially reducing the overall treatment time. By serving as a bridge to subsequent T Cell Directed therapy, this approach could enhance treatment outcomes and provide a more dynamic treatment pathway for patients with B-Cell Lymphoma.

What evidence suggests that this method is effective for B-cell lymphoma?

Research has shown that hyperfractionated radiation therapy can be effective for certain types of lymphoma, a kind of cancer. One study focused on primary cerebral lymphoma found that all patients' cancer became undetectable after receiving this treatment. Although this study involved a different type of lymphoma, it suggests that hyperfractionated radiation might also help treat diffuse large B-cell lymphoma (DLBCL). In this trial, all participants will receive dual hyperfractionated radiation therapy as a bridge to subsequent planned T Cell Directed therapy. These findings offer hope that this treatment could be useful when combined with therapies that redirect T-cells, a type of immune cell. ^{1 2 5 6 7}

Who Is on the Research Team?

Timothy J Robinson, MD PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for people with relapsed/refractory diffuse large B-cell lymphoma who are undergoing T-cell redirection therapies. Participants should meet specific health criteria to be eligible.

Inclusion Criteria

I can care for myself but may not be fully active.

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

I am not a candidate for intensive radiotherapy due to my condition or doctor's advice.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive dual fractionated radiation therapy as a bridge to T-cell directed therapy, with one area receiving once daily and the other twice daily radiation

Approximately 1 year

Follow-up

Participants are monitored for safety and effectiveness after radiation therapy

Approximately 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Hyperfractionated Dual Equivalent Fractionated Radiation Therapy

Trial Overview The study is testing a new radiation therapy method, comparing hypofractionated (fewer, larger doses) versus hyperfractionated (more, smaller doses) approaches in patients awaiting CAR T-cell therapy or bispecific antibodies.

How Is the Trial Designed?

Group I: Dual Hyperfractionated Radiation Therapy Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Published Research Related to This Trial

In a phase II trial involving 107 patients with high-risk, relapsed or refractory B-cell non-Hodgkin lymphoma, high-dose radioimmunotherapy (I-131-tositumomab) combined with chemotherapy before autologous stem-cell transplant showed promising long-term outcomes, with 10-year progression-free survival rates ranging from 43% to 64%.

The treatment was found to be feasible and safe, with a low non-relapse mortality rate of 2.8% at 100 days and similar toxicity profiles to standard regimens, suggesting that high-dose RIT could be a viable option alongside newer therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial evaluating the efficacy of high-dose Radioiodinated Tositumomab (Anti-CD20) antibody, etoposide and cyclophosphamide followed by autologous transplantation, for high-risk relapsed or refractory non-hodgkin lymphoma. Chow, VA., Rajendran, JG., Fisher, DR., et al.[2021]

The UK-FAST trial showed that a once weekly hypofractionated radiotherapy regimen (5 fractions of 5.7 Gy) for whole breast irradiation had similar toxicity levels compared to the conventional regimen (50 Gy in 25 fractions) over a 10-year follow-up, indicating it is a safe alternative.

The FAST-Forward trial demonstrated that a 5-fraction regimen (5.2 Gy per fraction) over one week is non-inferior in local control compared to the standard 40 Gy in 15 fractions over three weeks, supporting the efficacy of extreme hypofractionation in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Extreme hypofractionation: New indications for breast cancer radiotherapy]. Bockel, S., Louvel, G., Brion, T., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06898905?locStr=United+States&country=United+States&aggFilters=status%3A

Hyperfractionated Dual Equivalent Fractionated Radiation ... This study evaluates the feasibility and safety of a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation therapy ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/587538

Hyperfractionated Dual Equivalent Fractionated Radiation ... This study evaluates the feasibility and safety of a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation ...

3. trialx.com trialx.com/clinical-trials/listings/298532/hyperfractionated-dual-equivalent-fractionated-radiation-therapy/

Hyperfractionated Dual Equivalent Fractionated Radiation ... This study evaluates the feasibility and safety of a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated ...

4. trial.medpath.com trial.medpath.com/clinical-trial/961f2c81150d4e19/nct06898905-hyperfractionated-radiation-t-cell-lymphoma

Hyperfractionated Dual Equivalent Fractionated Radiation ... This study evaluates the feasibility and safety of a novel method for comparing the effectiveness of hypofractionated versus hyperfractionated radiation ...

5. withpower.com withpower.com/trial/phase-lymphoma-large-b-cell-diffuse-3-2025-a0aca

Radiation Therapy for B-Cell Lymphoma (HyDEF Trial) In a study of hyperfractionated radiation therapy for primary cerebral lymphoma, all patients achieved complete remission, but some experienced neurological ...

6. yalemedicine.org yalemedicine.org/clinical-trials/hydef

Hyperfractionated Dual Equivalent Fractionated (HyDEF) ... This study evaluates the feasibility and safety of a novel method for comparing the effectiveness of hypofractionated versus ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11646978/

Hyper-fractionated radiotherapy as a bridging strategy to ... In conclusion, bridging hyper-fractionated radiotherapy with CAR-T therapy is safe and effective for patients with relapsed/refractory diffuse large B-cell ...