Mogamulizumab + LD TSEBT for Cutaneous Lymphoma

Overseen By Zainab Ahmed

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must not be taking: Corticosteroids

Disqualifiers: Stage IA MF, CNS disease, Pregnancy, Autoimmune, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the efficacy of the combination of LD-TSEBT and mogamulizumab in patients with MF and SS. And to evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments before starting. For example, you need to stop retinoids and other systemic therapies at least 4 weeks before, and phototherapy at least 2 weeks before. However, some medications like stable doses of prophylactic antibiotics and certain corticosteroids are allowed.

What data supports the effectiveness of the treatment Mogamulizumab + LD TSEBT for Cutaneous Lymphoma?

Research shows that low-dose total skin electron beam therapy (LD-TSEBT) is effective in clearing skin disease in cutaneous T-cell lymphomas, and when combined with mogamulizumab, an antitumor immunotherapy, it may improve clinical outcomes for patients with challenging conditions like mycosis fungoides and Sézary syndrome. ^{1 2 3 4 5}

Is the combination of Mogamulizumab and Low-Dose Total Skin Electron Beam Therapy safe for humans?

Low-dose total skin electron beam therapy (TSEBT) has been shown to have minimal risk of acute toxicities (immediate side effects) and is considered safe for treating cutaneous lymphomas. Mogamulizumab, an antitumor immunotherapy, is noted for its long-term tolerability, suggesting it is generally safe for use in humans. ^{1 2 5 6 7}

How is the treatment Mogamulizumab + LD TSEBT different from other treatments for cutaneous lymphoma?

This treatment combines low-dose total skin electron beam therapy (LD-TSEBT), which effectively clears skin disease, with mogamulizumab, an antitumor immunotherapy that offers long-term tolerability. This combination aims to optimize clinical outcomes and provide a maintenance therapy option after achieving maximal response, which is unique compared to other treatments that often lack durable responses. ^{1 2 3 8 9}

Research Team

Youn H Kim, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults with stages 1B-IV Mycosis Fungoides or Sézary Syndrome who've had at least one prior treatment can join. They should be in decent health, with good organ function and no severe autoimmune diseases, HIV, HTLV-1, or active hepatitis. Pregnant women and those on high-dose steroids are excluded.

Inclusion Criteria

My liver is working well.

I had a stem cell transplant and don't have GvHD or need immunosuppressive therapy.

I haven't used any skin creams for my condition in the last 2 weeks.

Exclusion Criteria

I have HIV, HTLV-1, or active hepatitis B or C.

Pregnant or breastfeeding

I am on herpes medication for over 30 days with no recent outbreaks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mogamulizumab combined with low dose total skin electron beam therapy (LD TSEBT). LD TSEBT is initiated on Cycle 1 Day 2 over a 2 to 3 week period, and mogamulizumab is administered on specific days per cycle.

12 months

Cycle 1: 4 visits (in-person); Cycle 2 and beyond: 2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-related adverse events and progression-free survival.

12 months

Long-term follow-up

Participants' quality of life and time-to-next significant treatment are assessed over an extended period.

3 years

Treatment Details

Interventions

• Low-Dose Total Skin Electron Beam Tx (Radiation)
• Mogamulizumab (Monoclonal Antibodies)

Trial Overview The trial tests a combination of Mogamulizumab (an immunotherapy drug) and Low-Dose Total Skin Electron Beam Therapy (LD-TSEBT), which is a type of radiation therapy for skin involvement in these conditions to see how effective they are together.

Participant Groups

Group I: LD TSEBT Experimental Treatment 2 Interventions

Mogamulizumab with low dose total skin electron beam therapy. • LD (12 Gy) TSEBT will be initiated on Cycle 1 Day 2 (± 2 days) of mogamulizumab over 2 to 3 week period per standard of care (SOC), as tolerated. Mogamulizumab (1 mg/kg) will be administered over 60 minutes as follows (per SOC and FDA approved use in MF and SS): * Cycle 1 only: Days1; 8; 15; and 22 (± 2 days) * Cycle 2 and beyond: Day 1 and Day 15 (± 3 days)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

The combination of low-dose total skin electron beam therapy (LD-TSEBT) and mogamulizumab was well-tolerated and led to global complete responses in two patients with refractory Sézary syndrome, despite their previous treatments failing.

Both patients achieved significant clinical improvement, with one responding in 4 weeks and the other in 9 weeks, and maintained their complete responses for up to 72 weeks, suggesting this combination could be an effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome. Fong, S., Hong, EK., Khodadoust, MS., et al.[2022]

In a trial involving six patients with mycosis fungoides or Sézary syndrome, ultra-hypofractionated low-dose total skin electron beam therapy (TSEBT) was found to be a safe and feasible treatment, with most patients experiencing only mild side effects.

After 8 weeks of treatment, patients reported a significant improvement in their quality of life and a reduction in skin symptoms, indicating that this treatment regimen effectively addresses both tumor burden and patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma. Rolf, D., Elsayad, K., Eich, HT.[2021]

Total skin electron beam (TSEB) therapy is effective for treating primary cutaneous T-cell lymphoma (PCTCL), with overall response rates of 92% for mycosis fungoides (MF), 70% for Sézary syndrome (SS), and 89% for non-MF/SS patients.

While conventional dose regimens (30-36 Gy) showed a trend towards better overall survival and event-free survival compared to low-dose regimens (<30 Gy), low-dose TSEB was well tolerated with shorter treatment times and fewer adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total Skin Electron Beam for Primary Cutaneous T-cell Lymphoma. Elsayad, K., Kriz, J., Moustakis, C., et al.[2022]

In a study of 20 patients with cutaneous T-cell lymphoma, low-dose total skin electron beam therapy achieved a high overall response rate of 90%, indicating its effectiveness in treating skin lesions.

Patients experienced significant improvements in their quality of life, with a marked decrease in severity scores and skin-related quality of life measures lasting for a median duration of 21 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective observational trial of low-dose skin electron beam therapy in mycosis fungoides using a rotational technique. Newman, NB., Patel, CG., Ding, GX., et al.[2022]

In a study of 60 patients treated with total skin electron beam therapy (TSEBT) for primary cutaneous T-cell lymphoma, low-dose TSEBT (12 Gy) resulted in significantly fewer grade 2 acute adverse events compared to standard doses (30 Gy), indicating a safer treatment option.

Repeated low-dose TSEBT courses were found to be tolerable and did not increase the risk of acute adverse events, suggesting that this approach can be safely used for patients experiencing cutaneous relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities. Kroeger, K., Elsayad, K., Moustakis, C., et al.[2022]

In a study of 102 patients with mycosis fungoides treated with low-dose total skin electron beam therapy (TSEBT), overall response rates were high, reaching 90% for doses of 5 to <10 Gy, and 98% and 97% for doses of 10 to <20 Gy and 20 to <30 Gy, respectively.

The progression-free survival (PFS) rates for patients receiving lower doses (10 to <20 Gy and 20 to <30 Gy) were comparable to those receiving the standard higher dose (≥30 Gy), suggesting that lower doses may be an effective alternative with potentially reduced treatment-related toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting low-dose total skin electron beam therapy in mycosis fungoides. Harrison, C., Young, J., Navi, D., et al.[2011]

In a study of 21 patients with mycosis fungoides and Sézary syndrome, low-dose total skin electron beam therapy (TSEBT) resulted in a high overall response rate of 95%, with 57% achieving complete or very good partial responses.

The treatment was relatively safe, with only 60% of patients experiencing mild acute side effects, suggesting that low-dose TSEBT may allow for safer reirradiation during relapses compared to standard doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis. Kamstrup, MR., Gniadecki, R., Iversen, L., et al.[2022]

Total skin electron beam therapy (TSEBT) is highly effective for treating mycosis fungoides (MF), a type of cutaneous T-cell lymphoma, with conventional doses (30-36 Gy) leading to excellent skin responses, although most patients experience relapse.

Low-dose TSEBT (10-12 Gy) offers similar response rates and overall survival as conventional doses but with fewer side effects and shorter treatment times, making it a promising option for patients who may need repeated treatments after relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total skin electron beam therapy in mycosis fungoides-a shift towards lower dose? Chowdhary, M., Song, A., Zaorsky, NG., et al.[2019]

References

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

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma. [2021]

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

Total Skin Electron Beam for Primary Cutaneous T-cell Lymphoma. [2022]

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

Prospective observational trial of low-dose skin electron beam therapy in mycosis fungoides using a rotational technique. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Low-dose total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study. [2012]

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

Revisiting low-dose total skin electron beam therapy in mycosis fungoides. [2011]

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

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Total skin electron beam therapy in mycosis fungoides-a shift towards lower dose? [2019]