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

Trial Summary

What is the purpose of this trial?

This trial tests a combination of light therapy and a drug called POTELIGEO for patients with early-stage skin cancer. The light therapy aims to improve skin conditions, while POTELIGEO helps the immune system target and destroy cancer cells.

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.

What data supports the effectiveness of the drug mogamulizumab-kpkc for treating mycosis fungoides?

Research shows that mogamulizumab-kpkc significantly improves progression-free survival and overall response rates in patients with mycosis fungoides compared to another treatment, vorinostat. Additionally, combining mogamulizumab with phototherapy has shown greater antitumor activity in a mouse model, suggesting potential benefits for this combination in treating cutaneous T-cell lymphoma. ^{1 2 3 4 5}

Is the combination of Phototherapy and Mogamulizumab safe for treating Mycosis Fungoides?

Mogamulizumab has been shown to be generally safe in humans, but it can cause side effects like rash, fatigue, and infections. Serious reactions can occur, especially related to infections and skin issues, and it has specific warnings for use before certain transplants. ^{1 4 5 6 7}

How is the treatment of phototherapy combined with mogamulizumab unique for mycosis fungoides?

This treatment is unique because it combines phototherapy, which uses light to treat skin conditions, with mogamulizumab, a drug that targets specific receptors on cancer cells to enhance the immune system's ability to fight the disease. This combination aims to improve the effectiveness of treatment for advanced stages of mycosis fungoides, offering a novel approach compared to traditional therapies. ^{1 2 3 4 5}

Research Team

Lubomir Sokol, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. [2022]

3. Denmark 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. [2023]

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

FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sézary Syndrome. [2020]

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

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. [2021]

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

Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study. [2023]

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

Mogamulizumab Tops Standard of Care for CTCL. [2019]