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

Trial Summary

What is the purpose of this trial?

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).

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 data supports the effectiveness of the treatment Hyperfractionated Dual Equivalent Fractionated Radiation Therapy for B-Cell Lymphoma?

Research on hyperfractionated radiation therapy, a component of the treatment, shows it can improve outcomes by allowing higher doses without increasing side effects, as seen in studies on head and neck cancer and primary cerebral lymphoma. These studies suggest that hyperfractionation may enhance local control and survival rates compared to conventional radiation therapy. ^{1 2 3 4 5}

Is Hyperfractionated Dual Equivalent Fractionated Radiation Therapy safe for humans?

In a study of hyperfractionated radiation therapy for primary cerebral lymphoma, all patients achieved complete remission, but some experienced neurological deterioration and radiation brain injury, leading to the study's closure due to treatment toxicity. However, other reports suggest this regimen is generally free from significant harm. ^{2 6 7 8 9}

How is Hyperfractionated Dual Equivalent Fractionated Radiation Therapy different from other treatments for B-Cell Lymphoma?

Hyperfractionated Dual Equivalent Fractionated Radiation Therapy is unique because it involves giving smaller doses of radiation more frequently, which allows for higher total doses without exceeding the tolerance of the central nervous system. This approach aims to improve outcomes by reducing the risk of local relapse compared to conventional radiation therapy. ^{2 10 11 12 13}

Research Team

Timothy J Robinson, MD PhD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Altered fractionation in radiation therapy for squamous-cell carcinoma of the head and neck. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Phase I study of hyperfractionated whole brain irradiation (HWBI) in the treatment of primary cerebral lymphoma. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Altered fractionation in definitive irradiation of squamous cell carcinoma of the head and neck. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Altered fractionation schedules in radiation treatment: a review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Relation between Hypofractionated Radiotherapy, Toxicity and Outcome in Early Breast Cancer. [2018]

7. Ireland pubmed.ncbi.nlm.nih.gov

Ultrahypofractionated versus hypofractionated and conventionally fractionated radiation therapy for localized prostate cancer: A systematic review and meta-analysis of phase III randomized trials. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Extreme hypofractionation: New indications for breast cancer radiotherapy]. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort. [2022]

10. United States 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. [2021]

11. Romania pubmed.ncbi.nlm.nih.gov

The effects of ultrafractionated X-ray therapy in malignant lymphomas. [2007]

12. Thailand pubmed.ncbi.nlm.nih.gov

Importance of PET/CT scan use in planning radiation therapy for lymphoma. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Response to hyperfractionated accelerated radiotherapy in chemotherapy-refractory non-Hodgkin lymphoma. [2021]