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

(DLBCL Trial)

Recruiting in Durham (>99 mi)

+13 other 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

241 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II study will evaluate whether a reduction in radiation dose and field size will maintain a high rate of local control while minimizing the risk of acute and late toxicity . Hypothesis: The radiation dose and treatment volume can be safely reduced from 30 Gy to 20 Gy while maintaining high rates of local control in patients who had a negative PET-CT scan following rituximab - containing chemotherapy.

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 data supports the effectiveness of reduced-dose radiation therapy for diffuse large B-cell lymphoma?

Radiation therapy has shown improvement in progression-free survival for diffuse large B-cell lymphoma, and a trial is testing if a reduced dose can maintain long-term outcomes. Additionally, advanced techniques like image-guided radiotherapy (IGRT) can precisely target tumors, potentially reducing side effects. ^{1 2 3 4 5}

Is reduced-dose radiation therapy generally safe for humans?

Research on various forms of radiation therapy, like image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT), shows that these treatments are generally safe, with some risk of side effects such as gastrointestinal and genitourinary issues. These techniques are designed to target cancer more precisely, which helps protect healthy tissue and reduce side effects. ^{6 7 8 9 10}

How is reduced-dose radiation therapy unique for treating diffuse large B-cell lymphoma?

Reduced-dose radiation therapy for diffuse large B-cell lymphoma is unique because it aims to lower the radiation dose while maintaining effective long-term outcomes, potentially reducing side effects compared to traditional higher-dose radiation treatments. ^{2 3 11 12 13}

Research Team

Christopher Kelsey, MD

Principal Investigator

Duke Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Radiation treatment in non Hodgkin's lymphomas: present and future directions]. [2018]

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

A phase III randomized controlled trial of radiation dose optimization in non-Hodgkin lymphoma-diffuse large B-cell lymphoma (DOBL study): Study protocol and design. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The role of radiotherapy as salvage and/or consolidation treatment in relapsed/refractory and high-risk diffuse large B-cell lymphoma. [2019]

4. 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]

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

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer. [2011]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

7. England 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer. [2021]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021]

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

Limited-stage diffuse large B-cell lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy: involved-field versus involved-node radiotherapy. [2019]

12. Germany pubmed.ncbi.nlm.nih.gov

Patterns of failure of diffuse large B‑cell lymphoma patients after involved-site radiotherapy. [2018]

13. Greece pubmed.ncbi.nlm.nih.gov

A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. [2016]