Reduced-Dose Radiation Therapy for Diffuse Large B-cell Lymphoma

(DLBCL Trial)

Not currently recruiting at 15 trial locations

Overseen By Linda Kaltenbach, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must be taking: Rituximab

Disqualifiers: Primary CNS lymphoma, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lower dose of radiation can effectively control diffuse large B-cell lymphoma, a type of blood cancer, while reducing side effects. Patients who have completed at least three cycles of chemotherapy with rituximab and show no active cancer on a PET-CT scan will receive a reduced dose of radiation therapy. This study suits individuals who have finished chemotherapy and have no signs of active cancer on their scans. As an unphased trial, it provides a unique opportunity for patients to contribute to research that could enhance future treatment protocols.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this reduced-dose radiation therapy is safe for patients with diffuse large B-cell lymphoma?

Research has shown that using less radiation in treatment is safe for some lymphoma patients. For instance, one study found that low-dose radiation successfully controlled cancer in the treated area for five years in 98% of cases, meaning the cancer did not return where the radiation was applied.

Another study found that a lower radiation dose did not negatively affect long-term results for patients with diffuse large B-cell lymphoma (DLBCL), a type of cancer. This suggests that reducing the radiation dose can still be effective and may also reduce side effects.

Overall, these findings indicate that a lower radiation dose can be a safe option and might help lessen the side effects often seen with higher doses. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for diffuse large B-cell lymphoma, which often involves high-dose radiation and chemotherapy, this treatment approach uses a reduced-dose radiation therapy. Researchers are excited because this method administers radiation after just three cycles of rituximab-containing chemotherapy, potentially lowering the overall treatment burden. By delivering radiation in smaller, daily doses (1.5-2Gy) over a short period, this strategy aims to minimize side effects while maintaining effectiveness. The hope is to provide a gentler treatment option that still effectively targets the cancer.

What evidence suggests that reduced-dose radiation therapy is effective for diffuse large B-cell lymphoma?

Research has shown that using a lower radiation dose of about 20 Gy to treat diffuse large B-cell lymphoma (DLBCL) can still be very effective. In this trial, participants will receive radiation therapy at this reduced dose after completing three cycles of rituximab-containing chemotherapy. One study found that 98% of patients did not experience cancer recurrence in the treated area after five years. Another study confirmed these results, with 98.7% of patients free from cancer recurrence in the treated area after three years, and 97.4% after five years. Additionally, 91.7% of patients lived without cancer progression for three years. This evidence suggests that using a lower dose of radiation can effectively control the cancer while possibly reducing side effects. ^{2 6 7 8 9}

Who Is on the Research Team?

Christopher Kelsey, MD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

This trial is for adults with a type of cancer called diffuse large B-cell lymphoma. Participants must have completed certain chemotherapy, show no signs of cancer on recent PET-CT scans, and have adequate blood cell counts. Pregnant women and those with specific other lymphoma types or conditions that make radiation unsafe cannot join.

Inclusion Criteria

Signed study specific informed consent

Absolute neutrophil count greater than 1000 and platelet count greater than 40,000

My lymphoma is a specific type called DLBCL or high-grade B-cell lymphoma.

Exclusion Criteria

My lymphoma type is specifically listed in the WHO classification.

I have no health conditions that prevent me from receiving radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive at least 3 cycles of rituximab-containing chemotherapy

9-18 weeks

Weekly visits for chemotherapy administration

Radiation Therapy

Participants receive 19.5-20Gy of radiation therapy in 1.5-2Gy fractions, 5 days per week

2-3 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview The study is testing if lower doses of radiation therapy (20 Gy instead of the usual 30 Gy) can still effectively control this lymphoma without causing as many side effects. It's for patients who responded well to initial chemo treatments.

How Is the Trial Designed?

Group I: Single arm interventional study Experimental Treatment 1 Intervention

RT to 19.5-20Gy is given after 3 cycles of rituximab containing chemotherapy. RT is administered daily, 5 days per week in 1.5-2Gy fractions (treatments).

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

The Phase I study of 90Y-2IT-BAD-Lym-1 in patients with chemotherapy-resistant B-cell non-Hodgkin's lymphoma established a maximum tolerated dose (MTD) of 0.370 GBq/m2, with myelotoxicity being the primary dose-limiting factor, particularly thrombocytopenia.

Out of 8 patients treated, 5 showed a partial response or stabilization of their NHL, indicating that 90Y-2IT-BAD-Lym-1 may be an effective treatment option, warranting further clinical trials despite the need for bone marrow support during higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. O'Donnell, RT., Shen, S., Denardo, SJ., et al.[2016]

In a study of 551 low- and intermediate-risk prostate cancer patients treated with high-dose stereotactic body radiotherapy (SBRT), the treatment was well tolerated, with only 1.8% experiencing acute gastrointestinal toxicities and 10% experiencing acute genitourinary toxicities.

The 5-year cumulative incidence of prostate-specific antigen (PSA) failure was low at 2.1%, and 88% of patients who underwent biopsies after treatment showed no residual active disease, indicating effective tumor control with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer. Zelefsky, MJ., Pinitpatcharalert, A., Kollmeier, M., et al.[2021]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Patients with high-risk prostate cancer treated with image-guided intensity-modulated radiotherapy (IG-IMRT) experienced significantly lower rates of gastrointestinal (GI) toxicity (5.8%) compared to those treated with 3D conformal radiotherapy (3DCRT) (57.3%), indicating that IG-IMRT is a safer option.

Both IG-IMRT and 3DCRT showed similar rates of biochemical progression-free survival at 3 years (90.3% for IG-IMRT vs. 86.0% for 3DCRT), suggesting that while IG-IMRT reduces toxicity, it does not compromise treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Sveistrup, J., af Rosenschöld, PM., Deasy, JO., et al.[2021]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., 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]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

In a study of 22 patients with locally advanced rectal cancer, image-guided radiotherapy (IGRT) led to complete surgical resection in all cases, with 32% of patients showing no residual tumor after treatment.

The treatment was associated with minimal toxicity, although one patient experienced severe side effects likely due to an overdose of capecitabine, suggesting that IGRT is a promising approach for reducing complications in rectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer. Nguyen, NP., Ceizyk, M., Almeida, F., et al.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10171462/

Phase II Study of Dose-Reduced Consolidation Radiation ... Purpose: To evaluate the feasibility of reducing the dose of consolidation radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625001506

Long-term Update of a Phase 2 Study of Dose-Reduced ... Long-term results of this phase 2 study, with a median follow-up of 9 years, did not demonstrate late local failures when patients received ∼20 Gy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03681535

Dose-Reduced Consolidation Radiation Therapy in ... The 5-year local control rate was 98%. Progression-free and overall survival at 5 years was 81% and 88%. Therefore, there is emerging evidence of long term ...

4. medscape.com medscape.com/viewarticle/lower-dose-rt-effective-aggressive-lymphomas-2025a1000s41

Lower-Dose RT Effective in Aggressive Lymphomas At 3 and 5 years, the rates of freedom from local recurrence were 98.7% and 97.4%, progression-free survival rates were 91.7% and 87.2%, and ...

5. cancernetwork.com cancernetwork.com/view/radiation-therapy-in-diffuse-large-b-cell-lymphoma-a-little-boost-gets-you-over-the-finish-line

Radiation Therapy in Diffuse Large B-Cell Lymphoma R/R DLBCL is radiosensitive, and low-dose RT is sufficient to reprime the immune system and sensitize the lymphoma cells to CAR T-cell therapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6839887/

Associated Lymphoid Tissue (MALT) Lymphoma - PMC Overall, the outcomes among patients with extranodal MALT lymphoma are excellent with deaths due to disease occurring only rarely (4). While relapses after ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302625000717

Articles Low-dose moderate hypofractionated radiotherapy ... The regimen of 12 Gy in four fractions is safe and shows promising activity as a local treatment for patients with indolent non-Hodgkin lymphoma.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7941552/

A phase III randomized controlled trial of radiation dose ... This trial tests the efficacy of using reduced radiation dose in DLBCL without compromising on long‐term outcomes.

9. haematologica.org haematologica.org/article/view/11306

Outcomes of limited stage primary bone diffuse large B-cell ... The overall survival at 10 years was 77.9% in the RT group and 89.0% in the no RT group (P=0.42). The relapse-free survival at 10 years was 73.5% in the RT ...