Phototherapy + Mogamulizumab for Mycosis Fungoides

(PLIGHT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Lubomir Sokol, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

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

Breakthrough Therapy

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}

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Moffitt Cancer Center Tampa, FL

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute Lead Sponsor

Kyowa Hakko Kirin Pharma, Inc. Industry Sponsor

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] Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients' symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.

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

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. [2022] Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared.

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] Mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8-methoxypsoralen (8-MOP), followed by ultraviolet A (UVA) irradiation (PUVA therapy) is an effective phototherapy for early-stage MF. However, the efficacy of PUVA therapy for advanced-stage MF is not satisfactory, and the ideal combination partner for PUVA therapy has not yet been found. In this study, we developed a new mouse model of CTCL in which efficacy of PUVA was detected and further evaluated the efficacy of combination treatment of PUVA and mogamulizumab, an anti-CCR4 monoclonal antibody. Cytotoxicity of PUVA therapy against HH cells, a CTCL cell line, was observed in vitro. The cytotoxicity was dependent on both 8-MOP and UVA. Using HH cells, we developed a mouse model in which HH cells were subcutaneously inoculated in the ear. In this model, PUVA therapy suppressed tumour growth with statistical significance, while 8-MOP or UVA alone did not. Combination therapy of PUVA and mogamulizumab showed greater antitumor activity than either monotherapy with statistical significance. In the histological analysis of the tumour tissue, PUVA accelerated tumour necrosis and then induced the infiltration inflammatory cells in the necrotic area, suggesting that these cells served as effector cells for mogamulizumab. This combination therapy is expected to be a beneficial option for CTCL therapy.

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

FDA Approval Summary: Mogamulizumab-kpkc for Mycosis Fungoides and Sézary Syndrome. [2020] The FDA-approved mogamulizumab-kpkc, a CC chemokine receptor type 4 (CCR4)-directed mAb, in August 2018 for treatment of adult patients with relapsed or refractory mycosis fungoides or S&#233;zary syndrome after at least one prior systemic therapy. Regular approval was based on a randomized, open-label trial that randomized 372 such patients, with a median of 3 prior systemic therapies, to either mogamulizumab-kpkc or vorinostat. Investigator-assessed progression-free survival (PFS) was statistically significantly longer in the mogamulizumab-kpkc arm, which had an estimated median PFS of 7.6 months [95% confidence interval (CI), 5.6-10.2] compared with 3.1 months (95% CI, 2.8-4.0) in the vorinostat arm (HR = 0.53; 95% CI, 0.41-0.69). The confirmed overall response rate was 28% and 5%, respectively (P &lt; 0.001), based on global composite response criteria. Adverse reactions occurring in at least 20% of mogamulizumab-kpkc recipients included rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. Serious adverse reactions occurred in 36% of patients, most often from infection. The prescribing information includes warnings for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation, including severe and steroid-refractory graft-versus-host disease.See related commentary by Larocca et al., p. 7272.

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

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. [2021] Mogamulizumab-kpkc provides a novel mechanism of action for the treatment of mycosis fungoides and S&#233;zary syndrome. The efficacy and safety of mogamulizumab-kpkc for the treatment of relapsed or refractory mycosis fungoides and S&#233;zary syndrome were demonstrated in a multicenter, open-label, randomized phase III trial comparing mogamulizumab-kpkc with vorinostat. Patients treated with mogamulizumab-kpkc showed a statistically significant increased progression-free survival (PFS; 7.7 months) compared with vorinostat (3.1 months). Overall response rates were higher with mogamulizumab-kpkc compared with vorinostat (28% vs. 5%; p &lt; .0001). The most common adverse events (&gt; 20%) associated with mogamulizumab-kpkc include rash, infusion-related reaction, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. The use of mogamulizumab-kpkc up to 50 days prior to allogeneic hematopoietic stem cell transplantation has been associated with an increased risk of severe acute graft-vs.-host disease, steroid-refractory graft-vs.-host disease, and mortality. Additional labeled warnings include dermatologic toxicity, infection, and autoimmune complications. The overall benefit to risk assessment of mogamulizumab-kpkc is acceptable, but its use is constrained by the high cost of treatment and the short-term benefit.

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] Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF).

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

Mogamulizumab Tops Standard of Care for CTCL. [2019] In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.