Reduced Dose Radiotherapy for Non-Hodgkin's Lymphoma

Recruiting at 6 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Pregnancy, Nursing, T-cell lymphoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1-3 weeks

112 Participants Needed

Trial Summary

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Involved-site Radiation Therapy, Involved-field Radiation Therapy, Involved-site Radiotherapy (ISRT), Low-dose Radiation Therapy, Palliative Radiation Therapy for Non-Hodgkin's Lymphoma?

Research shows that low-dose radiation therapy can effectively relieve symptoms in patients with advanced or relapsed non-Hodgkin lymphomas, with response rates over 80% and symptom control lasting up to 2 years. Additionally, involved-site radiation therapy (ISRT) is designed to target the disease more precisely, reducing unnecessary exposure to healthy tissues. ^{1 2 3 4 5}

How is reduced dose radiotherapy different from other treatments for non-Hodgkin's lymphoma?

Reduced dose radiotherapy, specifically low-dose involved-site radiation therapy, is unique because it uses a much lower radiation dose (typically 4 Gy in two sessions) compared to standard treatments, which helps minimize side effects while still effectively controlling symptoms in patients with non-Hodgkin's lymphoma. ^{1 2 3 6 7}

What is the purpose of this trial?

This phase II trial compares the safety, side effects and effectiveness of reduced dose radiation therapy to standard of care dose radiation in treating patients with indolent non-Hodgkin lymphoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Standard of care radiation treatment for indolent non-Hodgkin lymphoma is usually delivered in 12 treatments. Studies have shown indolent lymphoma to be sensitive to radiation treatment, however, larger doses have higher rates of toxicities. A reduced radiation dose may be safe, tolerable and/or effective compared to standard of care radiation dose in treating patients with indolent non-Hodgkin lymphoma.

Research Team

Bradford S. Hoppe, MD, MPH

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with a slow-growing type of blood cancer called indolent non-Hodgkin lymphoma. It's specifically for those who have seen their disease return after treatment. Participants should be able to undergo radiation therapy and other imaging procedures like CT scans or PET scans.

Inclusion Criteria

Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only

Provide written informed consent

My lymphoma is a slow-growing type and has been confirmed by tests.

Exclusion Criteria

I am not willing to use birth control.

My condition is T-cell lymphoma.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit (in-person)

Treatment

Participants undergo reduced dose or standard of care radiation therapy

1-3 weeks

Daily visits (excluding weekends)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Visits at days 7 and 14, 3 months, then every 6 months

Treatment Details

Interventions

• Involved-site Radiation Therapy

Trial Overview The study is testing if giving a lower dose of radiation in just 3 treatments can be as effective and safer than the standard 12 treatments for this lymphoma. Patients will also undergo diagnostic tests, such as CT scans, endoscopic procedures, PET scans, and answer questionnaires.

Participant Groups

Group I: ARM 1 (reduced dose ISRT) Experimental Treatment 5 Interventions

Patients undergo reduced dose ISRT once daily (excluding weekends): 9 Gy delivered in 3 treatment fractions or 8 Gy in 2 fractions. At physician discretion, patients may receive 10 Gy in 5 fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.

Group II: ARM 2 (SOC ISRT) Active Control 5 Interventions

Patients undergo standard of care (SOC) radiation therapy once daily (excluding weekends): 24 Gy in 12 treatment fractions. Patients also undergo CT or PET/CT throughout the study. Patients may additionally undergo endoscopy during screening and during follow up.

Involved-site Radiation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Involved-site Radiation Therapy for:

• Indolent Non-Hodgkin Lymphoma
• Follicular Lymphoma
• Marginal Zone Lymphoma

Approved in United States as Involved-site Radiation Therapy for:

• Indolent Non-Hodgkin Lymphoma
• Follicular Lymphoma
• Marginal Zone Lymphoma

Approved in Canada as Involved-site Radiation Therapy for:

• Indolent Non-Hodgkin Lymphoma
• Follicular Lymphoma
• Marginal Zone Lymphoma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

Involved site radiation therapy (ISRT) is designed to treat lymphoma with a slightly larger volume than involved node radiation therapy, aiming to account for uncertainties in patient positioning and anatomical changes after chemotherapy.

The effectiveness of ISRT depends on various factors including the type of lymphoma, its stage, and the systemic therapy used, which helps in accurately targeting both visible and potential microscopic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involved Site Radiation Therapy in Adult Lymphomas: An Overview of International Lymphoma Radiation Oncology Group Guidelines. Wirth, A., Mikhaeel, NG., Aleman, BMP., et al.[2021]

Low-dose radiation therapy (typically 4 Gy in two fractions) has shown over 80% overall response rates in patients with advanced-stage or relapsed/refractory indolent non-Hodgkin lymphomas, providing effective palliation.

This approach maintains local control of the disease for up to 2 years, making it a promising option for patients with localized symptomatic disease while potentially reducing the toxicities associated with standard-dose radiation and systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Good things come in small packages: low-dose radiation as palliation for indolent non-Hodgkin lymphomas. Martin, NE., Ng, AK.[2019]

Low-dose involved-field radiation therapy (LD-IFRT) demonstrated a 75% overall response rate in 36 patients with advanced lymphoma, with 36% achieving complete remission lasting up to 31.3 months.

LD-IFRT is effective for both indolent and aggressive lymphoma subtypes, particularly showing an 86% response rate in non-diffuse large B-cell lymphoma, and it can be safely repeated at previously treated sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: a phase II study. Murthy, V., Thomas, K., Foo, K., et al.[2008]

A survey of 44 expert lymphoma radiation oncologists revealed significant variability in interpreting the newly developed involved-site radiation therapy (ISRT) guidelines, with only 3 out of 9 questions achieving over 70% agreement.

Despite all participants being familiar with ISRT, the lack of consensus indicates a need for clearer guidance on ISRT field design to ensure consistent application in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert radiation oncologist interpretations of involved-site radiation therapy guidelines in the management of Hodgkin lymphoma. Hoppe, BS., Hoppe, RT.[2016]

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 retrospective case series of 10 patients with advanced-stage low-grade non-Hodgkin's lymphoma, low-dose radiotherapy (2 x 2 Gy) resulted in high response rates, with 70% achieving complete response and 20% achieving partial response.

The treatment was well-tolerated, with minimal toxicity observed (no toxicity greater than grade 1), suggesting that low-dose radiotherapy is a safe and effective option for managing local symptoms in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of low-dose 2 x 2 Gy palliative radiotherapy in advanced low-grade non-Hodgkin's lymphoma. Ng, M., Wirth, A., Ryan, G., et al.[2018]

In a study involving 548 patients with indolent non-Hodgkin lymphoma, the standard treatment of 24 Gy in 12 fractions provided significantly better local control compared to the low-dose treatment of 4 Gy in two fractions, with a 2-year local progression-free rate of 94.1% versus 79.8%.

The 5-year follow-up confirmed that the 24 Gy treatment was more effective, with a hazard ratio of 3.46 indicating a much lower risk of local progression compared to the 4 Gy treatment, while also showing that the lower dose resulted in fewer side effects like alopecia and dry mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Hoskin, P., Popova, B., Schofield, O., et al.[2021]

References

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

Involved Site Radiation Therapy in Adult Lymphomas: An Overview of International Lymphoma Radiation Oncology Group Guidelines. [2021]

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

Good things come in small packages: low-dose radiation as palliation for indolent non-Hodgkin lymphomas. [2019]

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

Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: a phase II study. [2008]

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

Expert radiation oncologist interpretations of involved-site radiation therapy guidelines in the management of Hodgkin lymphoma. [2016]

5. 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]

6. Australia pubmed.ncbi.nlm.nih.gov

Value of low-dose 2 x 2 Gy palliative radiotherapy in advanced low-grade non-Hodgkin's lymphoma. [2018]

7. England pubmed.ncbi.nlm.nih.gov

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. [2021]