Topical JAK-Inhibition of Early-Stage CTCL

Phase 2Not Yet RecruitingNCT07781449

Aarhus University Hospital15 enrolled

Overview

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men or women aged 18 or older at the time of consent * Histologically confirmed diagnosis of mycosis fungoides (stage IA, IB, or IIA) * Stable disease requiring palliative treatment * No change in medication for 2 months prior to study entry * Willing and able to give informed consent, obtained prior to any study-related procedures Exclusion Criteria: * Hypersensitivity to the active substance or to any of the excipients (Benzyl alcohol, Butylhydroxyanisole, Cetostearyl alcohol) * Sézary syndrome (cancerous T-cells found in the blood) * Concomitant treatment with other topical/skin-directed therapies (phototherapy, radiotherapy, chlormethine gel, topical corticosteroids) * Psychiatric illness, disability, or social situation that would compromise subject safety or ability to provide consent * History of non-melanoma skin cancer (NMSC) * Atopic dermatitis or other clinically relevant dermatological diseases * Other clinically significant medical conditions, including: * Ongoing skin infections requiring antibiotics * Physical, laboratory, or vital sign abnormalities that would, in the investigator's opinion, put the subject at undue risk or interfere with interpretation of study results * Pregnancy or breastfeeding * Women of childbearing potential must use a highly effective contraceptive method

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Safety and Tolerability of Topical Delgocitinib]

Severity and causal relationship to study treatment will be assessed for all TEAEs and SAEs. Local tolerability will be evaluated based on application-site reactions. Vital signs, physical examination findings, and laboratory parameters will be assessed for clinically relevant abnormalities

Time frame: From baseline (day 0) to end of treatment week 16 (day 112)

Secondary Outcomes

Overall Response Rate (mSWAT)

Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD), based on clinical and molecular assessment using the modified Severity-Weighted Assessment Tool (mSWAT). The mSWAT is a clinician-assessed measure of skin disease burden calculated from body surface area (BSA) affected by patches, plaques, and tumors, weighted by lesion type (patch ×1, plaque ×2, tumor ×4). Scores range from 0 (no skin involvement) to a theoretical maximum of 400 (100% BSA, all tumor), with higher scores indicating more extensive/severe skin disease (worse outcome)

Time frame: From baseline (day 0) to end of treatment (day 112)

Change in Patient-Reported Pruritus (NRS)

Change from baseline in pruritus intensity, assessed using the Numeric Rating Scale (NRS), a patient-reported single-item scale ranging from 0 (no itch) to 10 (worst itch imaginable), with higher scores indicating greater itch severity (worse outcome).