Low Dose Radiation Therapy for Mantle Cell Lymphoma

Overseen By Bouthaina S Dabaja

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Scleroderma, Lupus, Uncontrolled hypertension, 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

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of an ultra-low dose of radiation for individuals with mantle cell lymphoma, a cancer affecting the lymph nodes. The trial examines using this low-dose radiation before or after targeted therapy that excludes chemotherapy. The aim is to determine if this approach can control the cancer with fewer side effects, allowing patients to undergo more frequent treatments. Individuals with a confirmed diagnosis of mantle cell lymphoma, whether newly diagnosed or previously treated, may qualify for this trial. As a Phase 2 trial, the research measures 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.

What prior data suggests that this low dose radiation therapy is safe for mantle cell lymphoma patients?

Research has shown that low-dose radiation therapy is generally safe for people with mantle cell lymphoma. Studies involving 591 patients found that this treatment caused very few serious side effects. It effectively shrank tumors and controlled the disease. Importantly, low-dose radiation can be administered multiple times without major issues, offering a flexible option for patients. This method results in fewer side effects compared to high-dose radiation, making it easier for patients to tolerate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Mantle Cell Lymphoma, which typically involve intense chemotherapy and stem cell transplants, low dose radiation therapy offers a gentler approach. This treatment is unique because it uses ultra low doses of radiation to target cancer cells directly before patients start chemotherapy-free targeted therapy. Researchers are excited about this method because it can potentially reduce side effects and improve patient quality of life while effectively managing the disease. Additionally, the ability to quickly assess the treatment's effectiveness and adjust the course if needed makes it a promising option for patients.

What evidence suggests that ultra low dose radiation therapy is effective for mantle cell lymphoma?

Research has shown that low-dose radiation therapy can effectively treat mantle cell lymphoma, a cancer affecting the lymphatic system. Studies have found that this cancer responds well to even small amounts of radiation. For example, one study found that 90% of patients were still alive a year after receiving low-dose radiation, and 55% did not experience cancer progression during that time. In this trial, participants will undergo ultra low-dose radiation therapy, which might also be effective for areas like the eyes affected by lymphoma. This method can be safer, with fewer side effects, allowing for more frequent treatments if needed. ^{1 3 4 6 7}

Who Is on the Research Team?

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with mantle cell lymphoma that has returned or isn't responding to treatment. They must have had at least two prior therapies, be in a stable condition (ECOG performance status of 2 or less), and have measurable disease. Women must not be pregnant and agree to birth control measures; men also need to use contraception if with a partner who can bear children.

Inclusion Criteria

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less than 3 x upper limit of normal or less than 5 x upper limit of normal if hepatic metastases are present.

My cancer has worsened after treatment with ibrutinib, shown by PET/CT scans.

Serum bilirubin less than 1.5 mg/dl.

Exclusion Criteria

I have an autoimmune disease that could make cancer treatment too risky.

I do not have any serious health conditions that my doctor thinks could make this study unsafe for me.

I've had radiation before where they now want to target, and more is unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo ultra low dose radiation for 1-2 days before chemotherapy free-targeted therapy. A second, longer course of radiation may be given if the lesion does not respond.

1-2 days

Chemotherapy-Free Targeted Therapy

Participants receive chemotherapy-free targeted therapy following ultra low dose radiation.

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 6 months for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Radiation Therapy

Trial Overview The study is testing ultra low dose radiation therapy before or after targeted therapy without chemotherapy in patients with relapsed/refractory mantle cell lymphoma. The goal is to see if this approach helps control the cancer better and improves responses compared to standard treatments.

How Is the Trial Designed?

Group I: Treatment (ultra low dose radiation therapy) Experimental Treatment 1 Intervention

Patients undergo ultra low dose radiation for 1-2 days before chemotherapy free-targeted therapy. Patients may receive a second, longer course of radiation if the lesion treated does not respond.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Radiotherapy (RT) is an effective treatment for mantle cell lymphoma (MCL), showing significant benefits even in low doses, and can help reduce the need for systemic therapies, especially in limited-stage MCL.

RT has a favorable safety profile and can be used as a palliative treatment in advanced-stage MCL, providing relief for patients who are heavily pretreated or resistant to chemotherapy, yet it remains underutilized in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy in mantle cell lymphoma: A literature review. Ben Barouch, S., Kuruvilla, J., Tsang, RW., et al.[2020]

Low-dose radiotherapy (LDRT) demonstrated a high overall response rate of 90% in treating low-grade lymphomas, with a median follow-up of 21 months, indicating its effectiveness as a primary treatment option.

LDRT was well-tolerated with no acute or long-term side effects reported, making it a safe treatment choice for patients, particularly those with smaller tumors (≤5 cm) and fewer previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response rates and recurrence patterns after low-dose radiotherapy with 4 Gy in patients with low-grade lymphomas. König, L., Hörner-Rieber, J., Bernhardt, D., et al.[2019]

Low-dose radiation therapy (LDRT) combined with chemotherapy showed an impressive complete response rate of 81% in 19 patients with relapsed, multiply refractory mantle cell lymphoma (MCL) after a median follow-up of 15.4 months.

LDRT was found to be safe, with no reported toxicities, and resulted in a 1-year overall survival rate of 90%, indicating its potential as an effective treatment option for patients with difficult-to-treat MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose radiation (4 Gy) with/without concurrent chemotherapy is highly effective for relapsed, refractory mantle cell lymphoma. Ning, MS., Pinnix, CC., Chapman, BV., et al.[2020]

In a study of 17 patients with indolent orbital lymphoma treated with ultra-low-dose radiation therapy (4 Gy in 2 fractions), 65% achieved a complete response, demonstrating the treatment's effectiveness in controlling the disease.

While oncologists reported minimal toxicity (6% grade 1), ophthalmologists noted a higher rate (33.3%) of new ocular toxicities post-treatment, indicating the need for careful monitoring of eye-related side effects in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High local control and low ocular toxicity using ultra-low-dose "boom-boom" radiotherapy for indolent orbital lymphoma. Shelukar, S., Fernandez, C., Bas, Z., et al.[2023]

In a study of 395 patients with mantle-cell lymphoma (MCL), common treatments led to frequent adverse events (AEs), with hypertension (40.5%), anemia (37.7%), and infections (36.1%) being the most reported.

Serious AEs like hepatotoxicity, stroke, and renal failure resulted in significant healthcare costs, highlighting the financial burden of managing these complications in MCL treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study. Kabadi, SM., Byfield, SD., LE, L., et al.[2021]

In a study of 255 patients with low-grade non-Hodgkin's lymphomas, chemoradiation treatment showed better total and relapse-free survival rates compared to chemotherapy alone.

Intensifying the components of the chemoradiation regimen further improved late outcomes, and complete remissions were identified as key predictors of survival, while local radiation therapy was effective for a small subset of patients with slow-progressing diffuse lymphocytic NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The radiation and chemoradiation treatments of generalized low-grade non-Hodgkin's lymphomas. 2. The late results]. Kharchenko, VP., Sotnikov, VM., Pan'shin, GA., et al.[2007]

In a study of 41 patients with mantle cell lymphoma, radiation therapy showed a high efficacy, with 69.1% of treated sites achieving a complete response and 23.5% a partial response, even in cases resistant to chemotherapy.

The research indicates that mantle cell lymphoma is sensitive to radiation, as evidenced by significant tumor response to relatively low doses (median 30.6 Gy), suggesting that radiotherapy could be a valuable treatment option for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy is an effective modality in the treatment of mantle cell lymphoma, even in heavily pretreated patients. Haque, W., Voong, KR., Shihadeh, F., et al.[2022]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6616267/

Low-dose radiation (4 Gy) with/without concurrent ... Low-dose radiation (4 Gy) with/without concurrent chemotherapy is highly effective for relapsed, refractory mantle cell lymphoma · Key Points. By ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25108680/

Radiation Therapy Is an Effective Modality in the Treatment ... Our data add to accumulating evidence that mantle cell lymphoma is a radio-sensitive disease with excellent responses to relatively low radiation doses, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2473952920306704

Low-dose radiation (4 Gy) with/without concurrent ... Overall survival at 1 year following initial LDRT was 90%, and 1-year progression-free survival following last course was 55%. In summary, LDRT ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02494700

NCT02494700 | Ultra Low Dose Orbital Radiation Therapy ... Using ultra low dose orbital radiation therapy may be effective in treating indolent B-cell lymphoma or mantle cell lymphoma involving the eye and may have ...

5. targetedonc.com targetedonc.com/view/lowdose-radiation-effective-withwithout-concurrent-chemotherapy-in-rr-mantle-cell-lymphoma

Low-Dose Radiation Effective With/Without Concurrent ... Low-dose radiotherapy of 4 Gy is both safe and effective as a treatment for relapsed/refractory patients with mantle cell lymphoma (MCL) across different sites ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427289/

Clinical Outcomes and Safety of Ultra-Low-Dose ... High response rates, favorable local control, and minimal severe toxicities were identified across ten studies including 591 patients. These ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.3221

Radiation therapy for patients with relapsed or refractory ... Low-dose RT for MCL appears to be very effective in this highly refractory population and should more often be considered as a palliative therapy.