EORTC 1820-CLTF: Open-Label, phase II, Multi-Center, study of Anti-CCR4 Monoclonal Antibody (mogamulizumab) Plus Total Skin Electron Beam therapy (TSEB) in patients with stage IB-IIB Cutaneous T-Cell Lymphoma (MOGAT)

The primary objective of this study is to evaluate the **progression-free survival** rate at 48 weeks in patients with stage IB-IIB **cutaneous T-cell lymphoma** treated with anti-CCR4 monoclonal antibody (mogamulizumab) and Total Skin Electron Beam therapy (TSEB). This objective is clinically relevant as it aims to determine the efficacy of the combined treatment in delaying disease progression, which is crucial for improving patient outcomes in this type of lymphoma.

Secondary objectives include:

• To evaluate the overall **safety** of the treatment regimen.
• To assess the **response rate** to the treatment.
• To assess the **progression-free survival** beyond the primary endpoint.
• To assess the **overall survival** of patients.
• To assess the **time to progression** of the disease.
• To evaluate the **duration of response** to the treatment.
• To evaluate the **time to next significant treatment**.

These secondary objectives are important for providing a comprehensive understanding of the treatment's impact on various clinical outcomes, including safety, efficacy, and long-term benefits for patients with cutaneous T-cell lymphoma.

The clinical trial involves a total of **6 participants** diagnosed with **cutaneous T-cell lymphoma**, specifically Mycosis Fungoides and Sézary Syndrome. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their diagnosis of Mycosis Fungoides at stages IB, IIA, or IIB, and all have previously failed at least one course of systemic therapy, excluding Psoralen plus ultraviolet light therapy (PUVA). The trial population is characterized by adequate hematological and organ function, and all participants have provided signed informed consent. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating a careful selection process to ensure participant safety and compliance with ethical standards.

The clinical trial is designed to evaluate the **progression-free survival** rate at 48 weeks in patients with stage IB-IIB **cutaneous T-cell lymphoma**, specifically focusing on the efficacy of the anti-CCR4 monoclonal antibody, **mogamulizumab**, in combination with Total Skin Electron Beam therapy (TSEB). This is a phase II, open-label, multi-center study. The trial employs a controlled design, although it is not double-blind, allowing for direct observation of treatment effects. The estimated duration of the trial is from February 2023 to September 2027, with participant involvement expected to last up to 48 weeks from the start of treatment.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), disease stage, prior systemic therapy failure, and adequate hematological and organ function. Following the screening, eligible participants will receive intravenous administration of mogamulizumab, with the maximum daily dose set at 1.0 mg/kg and a total dose not exceeding 40 mg/kg over the treatment period. The treatment period is capped at 18 weeks, with regular follow-up visits scheduled to monitor safety, response rate, and progression-free survival. The end-of-study visit will assess the primary endpoint of progression-free survival rate at 48 weeks, alongside secondary endpoints such as overall safety, response rate, and overall survival.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The study aims to provide comprehensive data on the safety and efficacy of mogamulizumab in combination with TSEB, contributing valuable insights into the management of cutaneous T-cell lymphoma.

The clinical trial involves the administration of **mogamulizumab**, an anti-CCR4 monoclonal antibody, as the experimental medication. Mogamulizumab is presented in a pharmaceutical form identified as PHF00230MIG. The medication is administered intravenously, with a dosage regimen of 1.0 mg/kg. The maximum total dose is capped at 40 mg/kg, and the treatment period extends up to 18 weeks. Mogamulizumab is indicated for the treatment of adult patients with mycosis fungoides or Sézary syndrome who have received at least one prior systemic therapy. The active substance, mogamulizumab, is a protein of non-human origin, and it is also known by the synonyms KW-0761 and AMG 761. The medication is classified under the ATC code L01XC25.

In addition to the experimental treatment, the study incorporates Total Skin Electron Beam therapy (TSEB) as a non-experimental treatment. TSEB is a standard-of-care therapy used in conjunction with mogamulizumab to evaluate the progression-free survival rate in patients with stage IB-IIB cutaneous T-cell lymphoma. The combination of mogamulizumab and TSEB aims to enhance therapeutic outcomes by leveraging the synergistic effects of the monoclonal antibody and radiation therapy. Participant compliance with the dosing schedule and treatment regimen is monitored throughout the study to ensure adherence and evaluate the efficacy and safety of the combined treatment approach.

Efficacy in this clinical trial will be assessed primarily through the **Progression Free Survival Rate** at 48 weeks after the initiation of treatment with mogamulizumab, as per the EORTC-ISCL-USCLC criteria. This primary endpoint will provide a measure of the time during which patients with stage IB-IIB cutaneous T-cell lymphoma remain free from disease progression. Secondary endpoints will include the overall safety of both mogamulizumab and Total Skin Electron Beam therapy (TSEB), the response rate to these treatments, progression-free survival, overall survival, time to progression, duration of response, and time to next treatment. Additionally, exploratory endpoints will evaluate quality of life using the Skindex-29 and EORTC-QLQ-C30 instruments, as well as time to treatment failure. These efficacy parameters will be measured and collected at specified time points, with the response rate being assessed from the start of treatment until 48 weeks after the last patient begins treatment. The analysis will involve determining the proportion of patients achieving partial or complete response according to the established criteria.