Deep Phenotyping of Cutaneous T Cell Lymphoma, Type Mycosis Fungoides
Condition: Mycosis Fungoides
MeSH terms: Mycoses; Mycosis Fungoides
Study type: Interventional

Summary: 
      Mycosis fungoides (MF) is an ultra-orphan disease of which the etiology remains unknown. MF
      is diagnosed by correlating clinical appearance with histopathological analysis of often
      multiple invasive skin punch biopsies. To move patient care and the development of novel
      treatments for MF forward, objective, sensitive and reliable tools that are preferably
      non-invasive are desired. Therefore, the objective of the current study is to phenotype the
      early stages of mycosis fungoides in detail and to assess the response of chlormethine (CL)
      gel monotherapy. With this approach the investigators aim to detect novel biomarkers and to
      establish methodologies for the (non-)invasive monitoring of MF.
    

Detailed description: 
      In recent years, knowledge about the wide spectrum of cutaneous T-cell lymphomas (CTCL) has
      broadened. Mycosis fungoides (MF) comprises about 50-70% of all primary cutaneous T-cell
      lymphomas (Willemze et al, 2019). Many CTCL are misdiagnosed due to clinical and
      histopathological similarity to other skin conditions (such as psoriasis vulgaris, atopic
      dermatitis and tinea corpora), low prevalence of disease and a lack of reliable tools for
      detection of these diseases, resulting in delayed diagnosis with years of discomfort and
      possibly a worse prognosis. Furthermore, standard treatment has never been proven curative,
      has many side effects and exacerbations are frequent. To date, the etiology of mycosis
      fungoides remains unknown and little research has been conducted into the mechanisms
      underlying its development and its response to treatment.

      Mycosis fungoides lesions change over time and differ between patients, consisting of three
      morphologically different stages: patches (erythematosquamous maculae), plaques
      (erythematosquamous, elevated and occasionally infiltrated lesions) and tumors (with or
      without ulceration). Only a relatively small group of patients advances to tumor stage MF
      during their lifetime. Mycosis fungoides is diagnosed by correlating clinical appearance with
      histopathological analysis of an invasive skin punch biopsy. Additionally, often multiple
      biopsies are required after diagnosis, e.g. when a lesion is clinically advancing to a
      different stage or if lesion origin is ambiguous. Currently no other biomarkers besides skin
      punch biopsies markers are available for the diagnosis of MF, the evaluation of a MF lesion
      over time, and the monitoring of a potential treatment effect. To advance MF patient care and
      the development of novel treatments for MF objective, sensitive and reliable (preferably
      non-invasive) tools are desired.

      Therefore, the objective of the current study is to evaluate disease-related characteristics
      and biomarkers, the intra- and inter-patient variability of biomarkers, to evaluate
      biomarkers for disease-monitoring following CL gel treatment and to investigate and monitor
      skin-related adverse events that might develop after CL gel application in MF patients. With
      this approach the investigators aim to detect novel biomarkers and to establish methodologies
      for the (non-)invasive monitoring of MF.

      For this purpose, a multi-modal patient profiling approach with in-depth characterization of
      cutaneous T-cell lymphomas will be performed. A clinical study will be conducted
      investigating the biology of the disease compared to healthy volunteers (part A) and
      patients' response to intervention (part B). The former to characterize objectively measured
      disease characteristics and mechanisms underlying its development, the latter to monitor the
      biomarker response associated to a MF-CTCL treatment, in this case CL gel. The study focusses
      on cellular, molecular, biophysical, imaging and microbiome analyses in comparison to healthy
      controls and between lesional and non-lesional skin of MF patients.
    

Intervention name(s): Chlormethine
Intervention type(s): Drug
Intervention description(s): Chlormethine gel 0.016%
Other intervention name(s): Ledaga; Valchlor
Intervention MeSH terms: Mechlorethamine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: This is an observational and interventional study in 20 Mycosis Fungoides patients and 10 healthy volunteers (observational only).
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mycosis Fungoides; Cutaneous T Cell Lymphoma; Biomarker; Chlormethine; Ledaga