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ClinicalTrials.gov ID

NCT07046663

Lead Sponsor

Fondazione Italiana Linfomi - ETSOTHER

Overall Status

Not yet recruiting

Study Type

Observational

Enrollment

190Estimated

Last Update Posted

Jul 4, 2025Actual

Start Date

Sep 2025Estimated

Primary Completion Date

Jun 2026Estimated

Completion Date

Jun 2026Estimated

Official Title

Long-term Assessment of Chlormethine Gel in Mycosis Fungoides: A Multicenter Retrospective Cohort Study

Brief Summary

The study aims to provide comprehensive insights into the long-term therapeutic outcomes, potential adverse effects, and overall patient experience with chlormethine gel, thereby informing clinical practice and guiding future treatment strategies for mycosis fungoides.

Detailed Description

Primary cutaneous lymphomas (PCLs) are a rare group of lymphoproliferative disorders with neoplastic lymphocyte proliferation in the skin. Cutaneous T-cell lymphomas (CTCL) make up 75% of PCLs, with mycosis fungoides (MF) being the most common. The cause of MF is unclear, but persistent antigenic stimulation and chronic inflammation may lead to neoplastic transformation. Pathogenesis involves genetic and epigenetic abnormalities, with a crucial role played by the skin microenvironment. Data from the International PROCLIPI registry (PROspective Cutaneous Lymphoma International Prognostic Index Validation and Evaluation) provide insight into the clinical management and outcomes of CTCL. This study has confirmed that early-stage disease has a relatively favorable prognosis, with a 5-year survival rate of about 90% for stage IA patients. Treatment is stage-dependent. Early stages are managed with skin-directed therapies (topical steroids, chlormethine and phototherapy) as first lines, while refractory or advanced disease requires systemic therapies such as interferon, bexarotene, and extracorporeal photopheresis. Chemotherapy and new monoclonal agents are used for refractory advanced cases. Topical chlormethine (TC) is an alkylating agent successfully used in treating CTCL since the 1950s. It works by a cytotoxic mechanism on DNA, altering the growth of neoplastic cells and enhancing the host's immunogenic potential. Initially, TC was packaged in an aqueous solution, but its use was limited by a high rate of skin hypersensitivity. In 2013, a multicenter, randomized, blinded phase II study compared 0.02% TC ointment with 0.02% TC gel, demonstrating the gel's non-inferiority to the ointment. The study also recorded longer and faster responses in the gel arm. No detectable systemic absorption of the drug was observed in patients' blood, consistent with previous case series. The evidence on the development of secondary neoplasms is controversial, particularly the risk of non-melanoma skin cancers (NMSC), which ranges from 0 to 9%. This risk is higher in patients previously treated with other modalities known to increase skin cancer incidence (e.g., radiotherapy and phototherapy). Melanoma development was reported by Ramsay et al. in a single patient with Fitzpatrick type I skin and a history of NMSC.

Real-world data from numerous studies have confirmed the efficacy of TC gel in treating early-stage MF and its use in combination with systemic therapies for advanced stages. In particular, the PROVE study, based on US real-world experience, demonstrated that modulating the TC schedule to every other day maintained good efficacy while reducing the incidence of adverse events, such as irritant contact dermatitis (ICD), and improving patient compliance. In a previous retrospective study on the first patients treated with TC gel in Italy, was showed that hyperpigmentation correlates with good response.

Currently, there is a lack of data on long-term response, recurrence rates after initial response, and the effect on treated areas considering the significant irritative response.

• Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

Yes

Eligibility Criteria

Inclusion Criteria:

• Patients age ≥ 18
• Histologically confirmed diagnosis of MF based on WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition
• Patients who are capable of understanding and willing, and able to read and write in Italian
• Patients who have signed informed consent form
• Patients who started treatment with chlormethine gel, from September 1, 2019 to September 30, 2024.
• Patients must have a minimum follow-up period of 6 months following the initiation of chlormethine treatment.
• Availability of complete medical records in order to provide protocol required variables.

Exclusion Criteria:

• Patients for whom retrospective data or information on the type of therapy, duration, and clinical outcomes are not available in the center's medical records.
• Refuse to sign a written informed consent.
• Patients not meeting the above-mentioned inclusion criteria

Observational Model

Cohort

Time Perspective

Retrospective

Lead Sponsor

Fondazione Italiana Linfomi - ETSOTHER

Collaborators

RECORDATI GROUPINDUSTRY

pvezzoli@asst-pg23.it

raffaella.sala@libero.it

marco.ardigo@hunimed.eu