PUVA Maintenance Therapy in Mycosis Fungoides
Condition: Patch/Plaque Stage Mycosis Fungoides
MeSH terms: Mycoses; Mycosis Fungoides
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to determine whether psoralen plus UVA (PUVA) photochemotherapy
      maintenance treatment prolongs disease-free survival of cutaneous T cell lymphoma (mycosis
      fungoides) patients.
    

Detailed description: 
      Background: Psoralen plus UVA (PUVA) photochemotherapy consists of the topical or oral
      application of psoralen, followed by exposure to UVA light. PUVA is used in various
      conditions, including early stages of mycosis fungoides (MF) and other primary and secondary
      lymphoproliferative disorders. PUVA has strong pro-apoptotic and immunomodulating properties,
      but the exact mechanisms by which PUVA leads to clearance of MF are not well understood.
      Although MF is generally a slowly progressing disease, it ultimately can spread to lymphoid
      tissues, peripheral blood, and other organs, leading to death.

      Previous Work: PUVA therapy is a well-accepted first-line treatment option for skin-limited
      MF (stages IA, IB, and IIA), leading to complete remission in a high portion of patients
      (approximately 70 to 90%). Long-term remissions can be achieved with PUVA in a certain
      percentage of patients. However, in most cases MF lesions relapse after stop of PUVA after
      variable time intervals with a median time to relapse of 14 to 17 month, according to our own
      experience. Not only is little is known about the therapeutic mechanisms of PUVA in MF but as
      little is known about optimal duration and frequency of treatment (2, 3, or 4 times weekly),
      dose escalation, and maintenance therapy. Although PUVA has been introduced more than 30
      years ago, there is lack of prospective controlled studies with clearly defined dose schemes
      and also an ongoing controversy whether PUVA maintenance therapy may prolong disease
      remission in MF upon initial complete clearance.

      Hypothesis & Intended Work: We hypothesize that PUVA prolongs disease free survival in MF
      patients. In a randomized multicenter trial involving 9 centers in Austria, we plan to
      investigate (1) the clinical efficacy of PUVA and its maintenance therapy in MF and, (2) the
      mechanisms by which PUVA leads to disease clearance. In total, 82 patients will be enrolled
      and treated with a defined PUVA regimen with 2 exposures per week for 12 to 24 weeks. After
      12 to 24 weeks of PUVA treatment, patients with complete remission will be randomized into
      two arms. In Arm A patients will be treated with PUVA maintenance therapy at constant single
      UVA doses. Maintenance treatment will be given once a week for one month (4 weeks), every 2
      weeks for 2 months (8 weeks) and after three months once a month over 6 months. After 9
      months of maintenance therapy patients will discontinue therapy. Patients in Arm B will
      receive no therapy. All patients will be followed until recurrence or at least 12 months (in
      non-recurrent patients) when the primary study analysis will be done. In addition, the
      follow-up will be extended to 60 months for long-term results.

      The mechanistic action of PUVA will be studied by laboratory investigations, including immune
      function and cytokine analysis.

      Outlook: A better understanding of the optimal regimen and the therapeutic mechanisms of PUVA
      in MF should help improving treatment strategies for this life-threatening disease. The
      understanding of the mode of action of PUVA in MF may also help to develop novel treatments
      using PUVA-affected pathways, allowing to achieve overall better long-term response and
      success.
    

Intervention name(s): 8-methoxypsoralen
Intervention type(s): Drug
Intervention description(s): 8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure
Other intervention name(s): Oxsoralen®; Gerot Pharmazeutika GmbH, Vienna, Austria
Intervention MeSH terms: Methoxsalen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mycosis fungoides; Psoralen and UVA (PUVA); Photochemotherapy; Maintenance treatment; Immune function