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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a lower dose of radiation is as safe and effective as the usual dose for treating indolent non-Hodgkin lymphoma, a slow-growing cancer. Involved-site Radiation Therapy, a form of radiation therapy, uses powerful rays to kill cancer cells and shrink tumors. The trial includes two groups: one receives a reduced radiation dose, and the other receives the standard dose. Individuals with certain types of indolent B-cell lymphoma, such as follicular or marginal zone lymphoma, who are experiencing disease progression might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that involved-site radiation therapy (ISRT) is generally well-tolerated by patients with non-Hodgkin lymphoma. Studies have found that this method can be effective while causing less damage to healthy tissues compared to other types of radiation.

The specific effects of lower dose radiation on normal tissues, especially in areas like the neck and chest, are not yet fully understood. However, lower doses are expected to reduce potential side effects while still effectively treating the cancer.

In summary, while exact safety data for lower doses is still being gathered, ISRT is already known for its effectiveness with fewer side effects. This suggests that using lower doses could be a safer option with even fewer side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-Hodgkin's lymphoma?

Researchers are excited about reduced dose Involved-site Radiation Therapy (ISRT) for Non-Hodgkin's Lymphoma because it offers a potentially safer and more convenient alternative to standard treatment options. While standard care typically involves a higher dose of radiation over many sessions, this approach uses significantly lower doses delivered in fewer sessions. This could mean less time spent in treatment and reduced side effects for patients. Additionally, even with the reduced dosage, the therapy still involves careful monitoring through CT or PET/CT scans to ensure effectiveness, making it a promising option for those seeking effective yet less burdensome treatment.

What evidence suggests that reduced dose radiation therapy might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that a slow-growing type of non-Hodgkin lymphoma responds well to radiation therapy. Involved-site radiation therapy (ISRT) targets only the cancer-affected areas and has proven effective with fewer side effects than older methods. This trial will compare two approaches: reduced dose ISRT and standard of care (SOC) ISRT. Studies suggest that a lower dose of ISRT can also be effective and cause even fewer side effects. For patients with early-stage lymphoma, using less radiation did not affect survival rates. This suggests that reduced dose ISRT, which participants in this trial may receive, could be a promising way to treat this type of cancer while minimizing harm. ^{2 3 6 7 8}

Who Is on the Research Team?

Bradford S. Hoppe, MD, MPH

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38631539/

Involved-site Radiation Therapy is Equally Effective and ... Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined ...

2. redjournal.org redjournal.org/article/S0360-3016(24)00514-5/fulltext

Involved-site Radiation Therapy is Equally Effective and ... Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854861/

Long-Term Results of IFRT vs. ISRT in Infradiaphragmal ... Our retrospective study aimed to compare the efficacy and side effects of involved-field (IFRT) versus involved-site radiotherapy (ISRT) fields ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0360301620309433

Involved Site Radiation Therapy in Adult Lymphomas This article presents a systematic overview of ISRT, updating key evidence and highlighting differences in the application of ISRT across the lymphoma clinical ...

5. ashpublications.org ashpublications.org/bloodadvances/article/3/9/1356/247084/Favorable-outcomes-with-de-escalated-radiation

Favorable outcomes with de-escalated radiation therapy for ... Key Points. Short-term data suggest that stage I/II NLPHL can be treated with ISRT without a negative impact on disease-free survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10741516/

Impact of Modern Low Dose Involved Site Radiation ... The effects of reduced prescription doses on normal tissue toxicity in the treatment of non-Hodgkin lymphomas of the neck/thorax region remain unclear.

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6283/505265/Ultra-Hypofractionated-Involved-Site-Radiation

Ultra-Hypofractionated Involved Site Radiation Therapy (ISRT ... Conclusions: Ultra-hypofractionated ISRT in the 'definitive' intent treatment of aggressive non-Hodgkin lymphomas has excellent local tumor ...

8. cancernetwork.com cancernetwork.com/view/s041-intensity-modulated-involved-site-radiation-therapy-non-hodgkin-lymphoma-head-and-neck

(S041) Intensity-Modulated Involved-Site Radiation ... Outcomes for head and neck NHL were maintained using ISRT with IMRT, with no marginal failures. ISRT reduces dose to normal tissues, and our results suggest ...