Topical JAK-Inhibition of Early-Stage CTCL

Mycosis Fungoides, Cutaneous T-cell Lymphoma

JAK inhibitor, Delgocitinib, Anzupgo, Early-stage mycosis fungoides, Cutaneous T-cell Lymphoma, Pan-JAK inhibitor

This study tests whether a cream named delgocitinib (Anzupgo), applied twice daily to the skin, is safe and well tolerated in people with early-stage cutaneous T-cell lymphoma (a rare type of skin cancer called mycosis fungoides). The cream works by blocking proteins called JAK enzymes, which are involved in inflammation and cancer cell growth in the skin. Delgocitinib cream is already approved for treating chronic hand eczema, but it has not yet been studied in people with cutaneous T-cell lymphoma. In this study, up to 15 participants with stable, early-stage disease will apply the cream to their affected skin for 16 weeks. Researchers will closely monitor for side effects and also look at whether the cream improves skin symptoms, such as itching and the appearance of the skin. Participants will be followed for 4 additional weeks after treatment ends. This is an early, exploratory study (a "proof-of-concept" trial) designed mainly to check safety, not to prove that the treatment works. The findings will help researchers decide whether to test this cream in larger studies in the future.

This is an investigator-initiated, descriptive, proof-of-concept, open-label, single-arm phase II pilot study evaluating topical Janus kinase (JAK) inhibition with delgocitinib 20 mg/g cream (Anzupgo) in adults with stable, early-stage mycosis fungoides (MF stage IA, IB, or IIA), the most common subtype of cutaneous T-cell lymphoma (CTCL). CTCL is a rare, incurable malignancy of unknown etiology. Dysregulated JAK/STAT signaling has repeatedly been linked to malignant T-cell proliferation, drug resistance, and skin barrier deterioration in CTCL. Delgocitinib is a pan-JAK inhibitor (JAK1, JAK2, JAK3, TYK2) already approved by the European Medicines Agency for chronic hand eczema, with a well-characterized local safety profile and minimal systemic absorption following topical application. This study investigates its off-label use in CTCL. Approximately 15 participants will complete an up-to 4-week screening phase, a 16-week treatment phase with delgocitinib applied topically twice daily to affected skin areas, and a 4-week observational follow-up phase, for a total study duration of approximately 24 weeks per participant. The primary objective is to evaluate the safety and tolerability of topical delgocitinib in this population, including incidence, severity, and causality of treatment-emergent adverse events and serious adverse events, local tolerability, and clinically relevant laboratory or vital sign abnormalities. The secondary objective is to explore preliminary evidence of clinical activity and biological effects, including overall response rate. Exploratory mechanistic analyses will be performed on lesional and non-lesional skin biopsies to characterize malignant T-cell populations, the tumor microenvironment, and skin barrier changes in response to treatment. There is no safety monitoring committee due to the small sample size; a certified dermatologist will monitor all adverse events, vital signs, and physical examination findings throughout the study. The study will be discontinued if more than three participants experience unacceptable adverse effects judged related to delgocitinib, or if more than seven participants experience disease progression requiring alternative therapy.

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