Phototherapy + Mogamulizumab for Mycosis Fungoides

(PLIGHT Trial)

Overseen By Richard Corona

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunomodulatory drugs, Photosensitizing medications

Disqualifiers: Large cell transformation, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with early-stage mycosis fungoides, a type of skin lymphoma. Researchers aim to evaluate the effectiveness and safety of using phototherapy (light treatment) alongside the medication mogamulizumab (also known as Poteligeo or mogamulizumab-kpkc). Participants with a confirmed diagnosis of mycosis fungoides, who have experienced stable disease or progression after prior therapies, and who are not currently experiencing severe skin conditions may be suitable candidates. The study is open to those who have previously tried other treatments. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires a 14-day period without previous CTCL therapy before starting treatment. If you're on a stable dose of low-dose systemic corticosteroids or certain topical medications, you may continue them, but the doctor will try to reduce the dose if possible. Other medications, especially those affecting the immune system or causing photosensitivity, may need to be stopped.

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

Research has shown that mogamulizumab, a treatment for mycosis fungoides (a type of skin cancer), can improve patient outcomes. Studies have found that it significantly increases the time patients live without disease progression and enhances the disease's response to treatment, suggesting the drug's general effectiveness.

Regarding safety, the FDA has already approved mogamulizumab for other uses, indicating it has passed safety checks for those conditions. However, using it with phototherapy (light treatment) is a newer approach. Early findings suggest this combination might be safe and tolerable, but further research is needed for confirmation.

For those considering joining a trial with this combination, it's important to know that these trials are in the early stages. Researchers are still assessing safety and side effects. Participants might face some risks, but current information suggests the treatment could be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Mogamulizumab-Kpkc (POTELIGEO) and phototherapy for treating Mycosis Fungoides because it offers a novel approach compared to current treatments. Most existing therapies, like topical steroids or chemotherapy, focus on reducing symptoms or slowing the disease progression. However, Mogamulizumab targets a specific protein on cancerous T-cells, potentially providing a more precise attack on the disease. When combined with phototherapy, which uses light to further target affected skin areas, this treatment could enhance effectiveness and reduce the overall burden of cancer cells more efficiently than current options.

What evidence suggests that this combination therapy could be effective for mycosis fungoides?

Research shows that mogamulizumab, also known as POTELIGEO, effectively treats advanced skin lymphomas, such as mycosis fungoides and Sézary syndrome. Mogamulizumab targets and destroys specific immune cells responsible for these diseases. In this trial, participants will receive a combination of mogamulizumab and phototherapy. Phototherapy uses light to treat skin problems and may enhance the effect of mogamulizumab in early-stage mycosis fungoides. Early results suggest this combination could be safe and effective. Although data for early-stage cases is limited, the interaction of these treatments shows promise. ^{1 3 4 6 7}

Who Is on the Research Team?

Lubomir Sokol, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with early-stage mycosis fungoides, a type of skin lymphoma. Participants must have had stable disease or some response to previous phototherapy and can't have had major surgery or certain treatments recently. They should not have severe illnesses, other cancers within the last 2 years (with exceptions), active infections like HIV or hepatitis, known allergies to study drugs, or be pregnant.

Inclusion Criteria

I have had previous treatments for my condition.

I am fully active or can carry out light work.

I have been on a stable low dose of corticosteroid for at least 4 weeks.

Exclusion Criteria

I've had a severe allergic reaction to POTELIGEO.

I have not had major surgery or radiation therapy in the last 4 weeks.

I was diagnosed with cancer in the last 2 years, but it's not active or one of the exceptions listed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive POTELIGEO (mogamulizumab-kpkc) for 8 cycles, with phototherapy starting after 2 cycles

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Mogamulizumab-Kpkc
• Phototherapy

Trial Overview The PLIGHT study tests combining phototherapy with an immunotherapy drug called Mogamulizumab in patients with early-stage mycosis fungoides. It's an open-label pilot study where all participants receive both treatments concurrently at a single center.

How Is the Trial Designed?

Group I: POTELIGEO & Phototherapy combination therapy Experimental Treatment 2 Interventions

POTELIGEO (mogamulizumab-kpkc) will be given according to FDA approved dose and scheduled for 8 cycles. After 2 cycles of POTELIGEO, all subjects will start phototherapy as combination therapy.

Mogamulizumab-Kpkc is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in United States as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Canada as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Japan as Poteligeo for:

• Adult T-cell leukemia/lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Kyowa Hakko Kirin Pharma, Inc.

Industry Sponsor

Trials

23

Recruited

1,600+

Published Research Related to This Trial

Mogamulizumab, a novel monoclonal antibody, effectively targets and treats mycosis fungoides and Sèzary syndrome by binding to C-C chemokine receptor 4, enhancing the immune system's ability to attack malignant T-cells.

In a real-life clinical setting in Italy, 12 patients with these skin lymphomas showed significant improvement in symptoms and quality of life when treated with mogamulizumab, indicating its efficacy and manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. Caruso, L., Castellino, A., Dessì, D., et al.[2022]

In a study of 122 patients with cutaneous T-cell lymphoma (CTCL), mogamulizumab demonstrated an overall response rate of 58.7%, with higher efficacy in Sézary syndrome (69.5%) compared to Mycosis Fungoides (46.0%).

Mogamulizumab was generally well-tolerated, with serious adverse reactions occurring in a small percentage of patients, including rash (8.1%) and infusion-related reactions (2.4%), indicating a favorable safety profile in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study. Beylot-Barry, M., Quereux, G., Nardin, C., et al.[2023]

In the phase III MAVORIC trial, patients with cutaneous T-cell lymphoma treated with mogamulizumab had significantly longer progression-free survival compared to those receiving vorinostat, a standard therapy.

Mogamulizumab also resulted in higher response rates and improved quality of life for patients, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab Tops Standard of Care for CTCL. [2019]

Mogamulizumab-kpkc significantly improves progression-free survival in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, showing a PFS of 7.7 months compared to 3.1 months with vorinostat in a phase III trial.

While mogamulizumab-kpkc is effective, it carries risks of serious side effects, including increased risk of severe acute graft-vs.-host disease and other complications, which must be weighed against its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. Watson, S., Marx, JB.[2021]

Mogamulizumab shows promising efficacy for patients with advanced cutaneous T-cell lymphomas, with a median progression-free survival (PFS) of 22 months based on a study of 21 patients followed for an average of 11.6 months.

The safety profile of mogamulizumab is considered acceptable, with 20 patients experiencing adverse events, of which only 10 were severe (grade III-IV), and the median time to the first adverse event was 21 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. Jouandet, M., Nakouri, I., Nadin, L., et al.[2022]

Mogamulizumab-kpkc, an FDA-approved treatment for relapsed or refractory mycosis fungoides or Sézary syndrome, significantly improved progression-free survival (PFS) compared to vorinostat, with a median PFS of 7.6 months versus 3.1 months in a study of 372 patients.

While mogamulizumab-kpkc showed a confirmed overall response rate of 28%, it also had notable adverse reactions, including rash and infections, with serious adverse reactions occurring in 36% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sézary Syndrome. Kasamon, YL., Chen, H., de Claro, RA., et al.[2020]

In a new mouse model of cutaneous T-cell lymphoma (CTCL), PUVA therapy (using 8-methoxypsoralen and UVA) significantly suppressed tumor growth, demonstrating its efficacy in treating early-stage mycosis fungoides (MF).

The combination of PUVA therapy with mogamulizumab, an anti-CCR4 monoclonal antibody, resulted in greater antitumor activity compared to either treatment alone, suggesting that this combination could be a promising option for advanced-stage MF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel mouse model of cutaneous T-cell lymphoma revealed the combined effect of mogamulizumab with psoralen and ultraviolet a therapy. Nakahashi, K., Nihira, K., Suzuki, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06235281

Phototherapy and Mogamulizumab in Early Stage MF ... Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Resolution of all clinically significant ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10889597/

Clinical and Real-World Effectiveness of Mogamulizumab Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T- ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00998

Mogamulizumab in Combination with Phototherapy for the ... Mogamulizumab in combination with phototherapy may be safe, tolerable, and/or effective in treating patients with stage IA-IIA MF. Eligibility Criteria ...

4. aetna.com aetna.com/cpb/medical/data/900_999/0940.html?ref=counterforcehealth.org

Mogamulizumab-kpkc (Poteligeo) - Medical Clinical Policy ... Combined Mogamulizumab and Total Skin Electron Beam Therapy for the Treatment of Mycosis Fungoides and Sezary Syndrome. Fong and colleagues (2020) stated ...

5. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2022/PC0244-Poteligeo_combined.pdf

Mogamulizumab (Poteligeo) patient input, indicated that some treatments (e.g., phototherapy, total skin electron beam therapy, extracorporeal phototherapy) for mycosis fungoides and ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602684/

Clinical Review - Mogamulizumab (Poteligeo) - NCBI - NIH The objective of the current review is to review the beneficial and harmful effects of mogamulizumab 1.0 mg/kg for the treatment of adults with relapsed or ...

7. withpower.com withpower.com/trial/early-phase-1-mycoses-1-2024-ddd23

Phototherapy + Mogamulizumab for Mycosis Fungoides Research shows that mogamulizumab-kpkc significantly improves progression-free survival and overall response rates in patients with mycosis fungoides compared ...