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A Multi-center, Randomized Study on Oral 8-methoxypsoralen Plus UVA With or Without Maintenance Therapy in Mycosis Fungoides EORTC/ISCL Stage IA to IIB

Phase 3
18 Years
82 Years
Open (Enrolling)
Patch/Plaque Stage Mycosis Fungoides

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Trial Information

A Multi-center, Randomized Study on Oral 8-methoxypsoralen Plus UVA With or Without Maintenance Therapy in Mycosis Fungoides EORTC/ISCL Stage IA to IIB

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 weeks. After 12
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. Thereafter, 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

Inclusion Criteria:

- Histopathologically documented MF clinical stage IA-IIB (see Table1) confirmed by
current or previous diagnostic lesion biopsy

- A Karnofsky performance score > 60

- No previous PUVA treatment

- Anti-ds-DNA (antinuclear antibodies) or anti-Ro/La antibodies: negative

- Acceptable organ function defined as follows:

SGOT (AST) and SGPT (ALT) < 2.5 times the upper limit of normal for the institution

- Creatinine < 2 times the upper limit of normal for the institution

- No evidence of severe cardiac insufficiency (NYHA grade III-IV)

- Women of child bearing potential must have a negative serum pregnancy test (ß-HCG)
within seven (7) days prior to randomization

- Absence of any serious intercurrent illness or infection at time of entry into the
study that could interfere with planned treatment

- Patients must be willing to accept limiting sun exposure on the day receiving PUVA

- Written informed consent

Exclusion Criteria:

- Pregnancy and Lactation

- Photosensitive diseases such as lupus erythematosus or basal cell nevus syndrome

- Skin cancer syndromes such as xeroderma pigmentosum or basal cell nevus syndrome

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recurrence after complete remission within 12 months post therapy

Outcome Description:

Recurrence is defined as mSWAT (modified severity weighted assessment tool ) >0. The primary outcome will be evaluated by survival analysis (log-rank test; Kaplan-Meier) comparing time to recurrence after complete remission between patients treated with maintenance therapy vs. patients without maintenance therapy.

Outcome Time Frame:

12 months after end of therapy

Safety Issue:


Principal Investigator

Peter Wolf, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Medical University of Graz


Austria: Federal Office for Safety in Health Care

Study ID:

EudraCT 2012-000212-28



Start Date:

February 2013

Completion Date:

October 2020

Related Keywords:

  • Patch/Plaque Stage Mycosis Fungoides
  • Mycosis fungoides
  • Psoralen and UVA (PUVA)
  • Photochemotherapy
  • Maintenance treatment
  • Immune function
  • Mycoses
  • Mycosis Fungoides