Low-Dose Radiation for Marginal Zone Lymphoma

Overseen By Jillian Gunther, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Other lymphoma, Scleroderma, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a very low dose of radiation can effectively manage marginal zone lymphoma, a type of low-grade cancer affecting white blood cells. Participants will initially receive Ultra Low Dose 4 Gy Radiation, with the possibility of a higher dose based on their disease response. The trial seeks individuals with stage I-II marginal zone lymphoma who are not planning to undergo other systemic cancer treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, it mentions that prior systemic therapy is allowed as long as it was given before the most recent disease assessment.

Is there any evidence suggesting that ultra-low dose radiation therapy is likely to be safe for humans?

Research has shown that ultra-low-dose 4 Gy radiation is usually well tolerated. Studies have found that patients with various types of marginal zone lymphoma, such as gastric MALT lymphoma and lung MALT, managed this treatment with few issues. These studies found it effective in controlling the disease while being gentle on the body.

Most patients did not experience severe side effects. The treatment was adjusted based on each patient's response, and many saw positive results after just the initial low dose. Even when more radiation was needed, patients responded well, and side effects remained manageable. This suggests that the treatment is quite safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for lymphoma?

Researchers are excited about the use of ultra low dose 4 Gy radiation for treating marginal zone lymphoma because it offers a gentler approach compared to conventional radiation therapies. Traditional treatments often involve higher doses of radiation, which can lead to more severe side effects. This new method uses significantly lower doses, potentially reducing harm to healthy tissues while still targeting cancer cells effectively. Additionally, this treatment is administered over just 1-2 days, offering a quicker and potentially more convenient option for patients.

What evidence suggests that ultra-low dose radiation might be an effective treatment for marginal zone lymphoma?

Research has shown that a very low dose of 4 Gy radiation can effectively treat marginal zone lymphoma (MZL). In studies, most patients fully responded to this initial low dose. Participants in this trial will receive this ultra-low dose of radiation therapy over 1-2 days. If the disease persists, a higher dose often leads to full recovery within a year. This method has proven both effective and manageable for patients, offering hope for managing MZL with fewer side effects. It has also succeeded in treating similar conditions, like certain stomach and lung lymphomas, suggesting it could work well for MZL too. ^{1 2 3 6 7}

Who Is on the Research Team?

Jillian Gunther

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage I-II marginal zone lymphoma who can sign consent. It's open to those who've had prior treatments but still show signs of the disease, and not planning systemic therapy before follow-up. Participants must use birth control if they can have children, and cannot join if they're pregnant or have certain psychiatric conditions that affect compliance.

Inclusion Criteria

I am not scheduled for any drug treatments before my first check-up after radiation.

I have had previous treatments for my condition, regardless of type or amount.

For patients with gastric MALT lymphoma, H. pylori testing is required

Exclusion Criteria

Patients living outside the US

I have had a condition where my lymphocytes grow abnormally.

I am currently being treated for active scleroderma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive ultra-low dose 4 Gy radiation therapy over 1-2 days

1-2 days

Response Evaluation

Participants' response to the initial radiation dose is evaluated to determine if additional radiation is needed

2-4 weeks

Additional Radiation (if needed)

Participants may receive an additional 12 Gy of radiation based on their response to the initial treatment

1-2 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of distant recurrence and in-field relapse at 24 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ultra Low Dose 4 Gy Radiation

Trial Overview The study tests ultra-low dose radiation therapy as a primary treatment for marginal zone lymphoma. Patients start with low doses which may be increased based on their response to the initial treatment, aiming to control the disease with minimal exposure.

How Is the Trial Designed?

Group I: Ultra Low Dose 4 Gy Radiation Experimental Treatment 1 Intervention

Participants will receive the ultra-low doses of radiation therapy over 1-2 days

Ultra Low Dose 4 Gy Radiation is already approved in United States, European Union for the following indications:

Approved in United States as Ultra Low Dose 4 Gy Radiation for:

• Marginal Zone Lymphoma (MZL)
• Gastric MALT Lymphoma

Approved in European Union as Ultra Low Dose 4 Gy Radiation for:

• Marginal Zone Lymphoma (MZL)
• Gastric MALT Lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 13 patients with primary BALT lymphoma treated with radiotherapy, there was a 100% response rate, with 67% achieving complete response, indicating that radiotherapy is highly effective for this rare cancer.

Very low-dose radiotherapy (4 Gy) resulted in a 60% complete response rate, while full-dose radiotherapy (24-36 Gy) had an 80% complete response rate, demonstrating that even lower doses can be effective and that the treatment is generally safe with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low-dose radiotherapy for extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue. Freret, ME., Tringale, KR., Boe, L., et al.[2023]

In a study of 250 patients with follicular or marginal zone lymphoma, very-low-dose radiotherapy (VLDRT) of 4 Gy resulted in a high overall response rate of 90%, with 68% achieving a complete response, demonstrating its efficacy in treating localized indolent non-Hodgkin lymphomas.

The 2-year cumulative incidence of local progression was 25% overall, but only 9% for patients receiving VLDRT as first-line treatment for potentially curable disease, suggesting that VLDRT is a safe and effective option that may reduce treatment duration and toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients? Imber, BS., Chau, KW., Lee, J., et al.[2022]

Localized low-dose radiotherapy (LDRT) has shown a 55% complete response rate in treating chemoresistant indolent non-Hodgkin's lymphomas, with effective doses as low as 4 Gy given in two fractions.

LDRT induces apoptosis in follicular lymphoma cells, which triggers an immune response involving macrophages and dendritic cells, suggesting a potential mechanism for its efficacy and a promising avenue for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized low-dose radiotherapy for follicular lymphoma: history, clinical results, mechanisms of action, and future outlooks. Ganem, G., Cartron, G., Girinsky, T., et al.[2010]

In a study involving 10 patients with localized pulmonary MALT lymphoma, treatment with very low radiation doses (2 × 2 Gy) delivered exclusively to tumor sites resulted in a 60% complete remission rate within the first 2 months.

The 5-year progression-free survival rate was 87.5%, indicating that this approach is not only effective but also safe, as all patients remained alive with no local progression observed during the median follow-up of 56 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients. Girinsky, T., Paumier, A., Ferme, C., et al.[2022]

In a study of 24 patients with orbital marginal zone lymphoma treated with 24-25 Gy of radiotherapy, all patients achieved a complete response, demonstrating the high efficacy of this treatment.

The study reported excellent long-term outcomes, with 100% overall survival and 90% freedom from progression at 2 years, while noting that aside from cataract formation, there was minimal late toxicity associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of low dose radiotherapy for primary orbital marginal zone lymphoma. Tran, KH., Campbell, BA., Fua, T., et al.[2019]

In a study of 7 patients with low-grade orbital lymphomas treated with ultra-low dose radiotherapy (ULDRT), there was a remarkable local control rate of 100%, with 71% achieving a complete response after a median follow-up of 22 months.

The treatment was associated with minimal toxicity, with only mild side effects like dry eye and pruritus reported, making ULDRT a promising option for managing indolent orbital lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-low dose radiotherapy in the management of low-grade orbital lymphomas. de Castro, B., Peixeiro, RP., Mariz, JM., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38843856/

Response-adapted ultra-low-dose 4 Gy radiation as ... - PubMed Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial · Authors.

2. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00211-2/fulltext

Ultra–Low-Dose Radiation for Extranodal Marginal Zone ... ULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT. Introduction. Extranodal marginal zone ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624001339

Response-adapted ultra-low-dose 4 Gy radiation as ... Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months.

4. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00133-9/abstract

Response-adapted ultra-low-dose 4 Gy radiation as ... Long-term outcomes and patterns of relapse of early-stage extranodal marginal zone lymphoma treated with radiation therapy with curative intent.

5. redjournal.org redjournal.org/article/S0360-3016(23)06159-X/fulltext

Ultra Low-Dose Radiation for Extranodal Marginal Zone ... With this approach, patients receive initial treatment with 4 Gy, and additional RT is considered for those with persistent or locally progressive disease.

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2821030

Response-Adapted Ultralow-Dose Radiation Therapy for ... Response-adapted ultralow-dose radiation therapy is an effective approach for indolent orbital B-cell lymphoma, conferring high rates of local control.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39524525/

Ultra-Low-Dose Radiation for Extranodal Marginal Zone ... ULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT.