An Investigator Initiated, descriptive, proof-of-concept, open-label pilot study targeting the tumor microenvironment and skin barrier deficiency through JAK1/3 inhibition

The primary objective of this study is to evaluate whether treatment with **Xeljanz** (tofacitinib) decreases disease activity in patients with **Mycosis Fungoides**, a type of cutaneous T-cell lymphoma. This is clinically relevant as Mycosis Fungoides is a chronic and progressive condition, and reducing disease activity could potentially improve patient outcomes and quality of life. The study aims to target the tumor microenvironment and address skin barrier deficiencies through the inhibition of **JAK1/3** pathways, which are implicated in the pathogenesis of this disease.

The clinical trial involves participants diagnosed with **Mycosis Fungoides**, specifically those in stages IA, IIA, and IIB. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a stable disease with no change in medication for at least two months or five half-lives prior to study entry. The trial excludes vulnerable populations and requires participants to have a histologically confirmed diagnosis. General health status criteria include an **alanine transaminase** (ALT) level of ≤ 2.5 times the institutional upper limit of normal (ULN), serum creatinine ≤ 1.5 x ULN, and a negative test for tuberculosis, HIV, hepatitis B, and C. Participants must have received the yearly flu vaccine and COVID-19 recommended vaccines. Additionally, they must have an absolute neutrophil count of ≥ 1 x 10^3/µL, platelets ≥ 100 x 10^3/µL, hemoglobin level ≥ 5.5 mmol/L, and bilirubin level ≤ 1.5 times the institutional ULN. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the requirement for women of childbearing potential and men to use safe contraception methods during the study and for a minimum of four weeks after the termination of treatment. Participants must be willing to participate, capable of giving informed consent, and the consent must be obtained prior to any study-related procedures.

The clinical trial is a Phase 4, open-label pilot study designed to evaluate the efficacy of **tofacitinib** in patients with **Mycosis Fungoides**. The trial aims to assess whether treatment with Xeljanz decreases disease activity. The study is expected to run from October 2022 to December 2024, with a maximum treatment period of 8 weeks for each participant. The trial involves oral administration of Xeljanz 10 mg film-coated tablets, with a maximum daily dose of 20 mg. Participants will be required to meet specific inclusion criteria, such as being 18 years or older, having a histologically confirmed diagnosis of Mycosis Fungoides, and maintaining stable disease without medication changes for at least two months prior to study entry.

The trial design includes several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor response to treatment and safety. The primary endpoint is to evaluate the complete response, partial response, stable disease, or progressive disease, and the overall response rate to treatment. Participants will be involved in the study for the duration of the treatment period, with additional follow-up visits as necessary. The end-of-study visit will conclude the participant's involvement, assessing the final treatment outcomes and any adverse events.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study is not categorized as low intervention, as it tests Xeljanz for a new indication despite its prior approval in Europe. The trial is conducted under strict adherence to ethical guidelines, ensuring informed consent is obtained from all participants before any study-related procedures are initiated.

The clinical trial involves the administration of **XELJANZ** 10 mg film-coated tablets, which contain the active substance **tofacitinib**. Tofacitinib is a chemical compound, also known by its synonyms CP-690,550 and TASOCITINIB. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The maximum daily dose of XELJANZ is 20 mg, with a total maximum dose of 20 mg per day. The treatment period is limited to a maximum of 8 weeks. The medication is manufactured by Pfizer Europe MA EEIG and is identified by the marketing authorization number EU/1/17/1178/006. The ATC code for tofacitinib is L04AA29, indicating its classification as an immunosuppressant.

In this study, XELJANZ is the experimental treatment, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified. The trial is designed to assess the effect of JAK1/3 inhibition on disease activity, specifically targeting the tumor microenvironment and skin barrier deficiency. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by evaluating the response to treatment with Xeljanz in patients with **Mycosis Fungoides**. The primary endpoints include the assessment of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), as well as the overall response rate to the treatment. These parameters will be measured to determine the effectiveness of the intervention in reducing disease activity. The trial is designed as an open-label pilot study, focusing on the tumor microenvironment and skin barrier deficiency through JAK1/3 inhibition. The study will involve adult participants who meet specific inclusion criteria, such as having a histologically confirmed diagnosis of Mycosis Fungoides and stable disease. The trial is set to conclude by the end of 2024, with the treatment period lasting up to 8 weeks. The efficacy assessments will be conducted throughout the study to monitor the participants' response to the treatment regimen.