Mogamulizumab + LD TSEBT for Cutaneous Lymphoma

Overseen By Zainab Ahmed

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Corticosteroids

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with certain types of skin lymphoma, specifically mycosis fungoides (MF) and Sézary syndrome (SS). Researchers aim to assess the effectiveness and safety of combining low-dose skin radiation, known as Low-Dose Total Skin Electron Beam Therapy, with the drug mogamulizumab. The trial seeks participants who have advanced stages of MF or SS (beyond early-stage IB-IV), have tried at least one other treatment, and are not currently experiencing severe treatment side effects. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant advancements in treatment.

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.

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

Research shows that mogamulizumab is generally well-tolerated by patients with Mycosis Fungoides (MF) and Sézary Syndrome (SS). Studies have found that it maintains a consistent safety record over five years, indicating manageable side effects. Common side effects might include skin rash and infusion reactions, but these are usually mild.

For Low-Dose Total Skin Electron Beam Therapy (LD-TSEBT), research indicates it is effective and safe, particularly for treating skin lymphomas (a type of skin cancer). The treatment is generally well-tolerated, with side effects that are often mild and short-lived.

Both treatments have demonstrated safety and manageability for patients with similar conditions, suggesting they are likely to be well-tolerated when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for cutaneous lymphoma, like chemotherapy or phototherapy, work by targeting and destroying rapidly dividing cells or using light to kill cancer cells. But Mogamulizumab works differently, targeting a specific protein called CCR4 on cancerous T-cells, which makes it a targeted therapy. Researchers are excited because combining Mogamulizumab with low-dose total skin electron beam therapy (LD TSEBT) may enhance the overall effectiveness and provide more precise treatment, potentially leading to better outcomes with fewer side effects. This approach offers a promising alternative for patients whose conditions haven't responded well to conventional therapies.

What evidence suggests that the combination of LD-TSEBT and mogamulizumab could be effective for cutaneous lymphoma?

Research has shown that mogamulizumab can extend the lives of people with advanced cutaneous T-cell lymphoma, a type of skin cancer. Studies have found that patients treated with mogamulizumab live longer than those receiving other treatments. Additionally, low-dose total skin electron beam therapy (TSEBT) effectively reduces symptoms in mycosis fungoides and Sézary syndrome, both types of skin lymphoma. In this trial, participants will receive a combination of mogamulizumab and low-dose TSEBT. These treatments complement each other: mogamulizumab targets and kills cancer cells, while TSEBT reduces skin lesions. Together, they offer a promising approach for patients with these conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Youn H Kim, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Low-Dose Total Skin Electron Beam Tx
• Mogamulizumab

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.

How Is the Trial Designed?

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)

Low-Dose Total Skin Electron Beam Tx is already approved in United States, European Union for the following indications:

Approved in United States as Low-Dose Total Skin Electron Beam Therapy for:

• Mycosis fungoides
• Sézary syndrome
• Cutaneous T-cell lymphoma

Approved in European Union as Low-Dose Total Skin Electron Beam Therapy for:

• Mycosis fungoides
• Sézary syndrome
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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 10 patients with stage IB-IV mycosis fungoides, low-dose total skin electron beam therapy (10Gy) resulted in a high overall response rate of 90%, with 70% achieving complete or very good partial responses.

The treatment was well tolerated, with mostly mild to moderate side effects, and the median duration of response was 5.2 months, suggesting that low-dose TSEBT could be a viable option for managing cutaneous T-cell lymphoma.

NCBI (Pubmed)

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. Kamstrup, MR., Lindahl, LM., Gniadecki, R., et al.[2012]

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 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]

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]

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]

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 (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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25476993/

Low-dose total skin electron beam therapy as an effective ... Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109424000654

Fine-Tuning Low-Dose Total Skin Electron Therapy for ... Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden.

3. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00065

Low-Dose Total Skin Electron Beam Radiotherapy in Stage ... This study investigates whether low-dose total skin electron beam therapy (TSEBT) at 8-12 Gy improves outcomes in stage IB to IIB mycosis ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11997445/

Total skin electron beam therapy - PMC Total skin electron beam therapy (TSEBT) is probably the most effective skin directed therapy for widespread primary cutaneous lymphomas.

5. jaad.org jaad.org/article/S0190-9622(14)02059-3/fulltext

Low-dose total skin electron beam therapy as an effective ... Low-dose total skin electron beam therapy can rapidly reduce the burden of skin disease in mycosis fungoides. Mycosis fungoides (MF) is the most ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9786352/

Short‐term efficacy and safety of total skin electron beam ... TSEBT is an associated with an excellent short term safety profile. Both schedules show high ORR, with standard dose TSEBT demonstrating highest CRR.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623002158

Ultrahypofractionated Low-Dose Total Skin Electron Beam ... TSEBT with 8 Gy in 2 fractions achieves good disease control and symptom palliation with acceptable toxicity, greater convenience, and fewer hospital visits.