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

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 Low Dose Radiation Therapy for Mantle Cell Lymphoma?

Research shows that low-dose radiation therapy can be effective for mantle cell lymphoma, with high complete response rates and minimal side effects. In one study, 81% of patients with relapsed, refractory mantle cell lymphoma achieved complete response after low-dose radiation, even when other treatments had failed. ^{1 2 3 4 5}

Is low dose radiation therapy safe for humans?

Research on low dose radiation therapy for low-grade lymphomas, including mantle cell lymphoma, shows it is generally safe with minimal side effects. Studies report high response rates and low toxicity, with no severe side effects observed. ^{1 5 6 7 8}

How does low-dose radiation therapy differ from other treatments for mantle cell lymphoma?

Low-dose radiation therapy for mantle cell lymphoma is unique because it uses a lower dose of radiation to effectively control the disease, even in patients who have not responded to other treatments. It is particularly beneficial for those who are heavily pretreated or have relapsed, as it can be safely combined with chemotherapy and repeated without significant side effects. ^{1 2 3 5 9}

What is the purpose of this trial?

This phase II trial studies how well ultra low dose radiation works before or after chemotherapy-free targeted therapy in treating patients with mantle cell lymphoma that has come back or does not respond to treatment. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Ultra low dose radiation is generally associated with a lower risk of side effects which may allow patients to be able to receive low-dose radiation therapy more often than high-dose radiation therapy. This trial may help doctors learn if giving ultra low dose radiation helps control mantle cell lymphoma and improves response to chemotherapy free targeted therapy.

Research Team

Bouthaina S. Dabaja

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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 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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Ultra-low dose radiotherapy in the management of low-grade orbital lymphomas. [2022]

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

Radiation therapy is an effective modality in the treatment of mantle cell lymphoma, even in heavily pretreated patients. [2022]

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

Low-dose radiation (4 Gy) with/without concurrent chemotherapy is highly effective for relapsed, refractory mantle cell lymphoma. [2020]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The radiation and chemoradiation treatments of generalized low-grade non-Hodgkin's lymphomas. 2. The late results]. [2007]

5. 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]

6. Germany pubmed.ncbi.nlm.nih.gov

Response rates and recurrence patterns after low-dose radiotherapy with 4 Gy in patients with low-grade lymphomas. [2019]

7. Greece 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. [2021]

8. China pubmed.ncbi.nlm.nih.gov

High local control and low ocular toxicity using ultra-low-dose "boom-boom" radiotherapy for indolent orbital lymphoma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Radiotherapy in mantle cell lymphoma: A literature review. [2020]