PUVA Maintenance Therapy in Mycosis Fungoides
Information source: Medical University of Graz
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Patch/Plaque Stage Mycosis Fungoides
Intervention: 8-methoxypsoralen (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Medical University of Graz Official(s) and/or principal investigator(s): Peter Wolf, MD, Principal Investigator, Affiliation: Medical University of Graz
Overall contact: Peter Wolf, MD, Phone: +43 316 385, Ext: 80315, Email: peter.wolf@medunigraz.at
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.
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Recurrence after complete remission within 12 months post therapy
Secondary outcome: Quality of lifeHADS Cytokine response in serum Levels of regulatory T cells Function of regulatory T cells Microscopic alterations Cytokine expression in the skin
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 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
success.
Eligibility
Minimum age: 18 Years.
Maximum age: 82 Years.
Gender(s): Both.
Criteria:
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
treatment
- 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
Locations and Contacts
Peter Wolf, MD, Phone: +43 316 385, Ext: 80315, Email: peter.wolf@medunigraz.at
Medical University of Graz, Graz 8010, Austria; Recruiting Peter Wolf, MD, Phone: +43 316 385, Ext: 80315, Email: peter.wolf@medunigraz.at Regina Fink-Puches, MD, Phone: +43 316 385, Ext: 12371, Email: regina.fink@medunigraz.at Peter Wolf, MD, Principal Investigator Regina Fink-Puches, MD, Sub-Investigator
Department of Dermatology, Medical University of Innsbruck, Innsbruck A-6020, Austria; Not yet recruiting Gudrun Ratzinger, MD, Phone: +43 512 504, Ext: 81484, Email: gudrun.ratzinger@i-med.ac.at Matthias Schmuth, MD, Phone: +43 512 504 Matthias Schmuth, MD, Principal Investigator Gudrun Ratzinger, MD, Sub-Investigator
Department of Dermatology, General Hospital of the City of Linz, Linz A-4021, Austria; Not yet recruiting Josef Auböck, MD, Phone: +43 732 7806, Ext: 3732, Email: josef.auboeck@akh.linz.at Christine Scheurecker, MD, Phone: +43 732 7806, Ext: 3732, Email: christine.scheurecker@akh.linz.at Josef Auböck, MD, Principal Investigator Christine Scheurecker, MD, Sub-Investigator Susanne Gross, MD, Sub-Investigator
Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University, Salzburg A-5020, Austria; Not yet recruiting Helmut Hintner, MD, Phone: +43 662 4482, Ext: 3001, Email: h.hintner@salk.at Sylvia Selhofer, MD, Phone: +43 662 4482, Ext: 3001, Email: S.Selhofer@salk.at Helmut Hintner, MD, Principal Investigator Sylvia Selhofer, MD, Sub-Investigator
Department of Dermatology, County Hospital St. Pölten, St. Pölten A-3100, Austria; Not yet recruiting Franz Trautinger, MD, Phone: +43 2742 300, Ext: 11906, Email: franz.trautinger@meduniwien.ac.at Susanne Eder, MD, Phone: +43 2742 300, Ext: 11906 Franz Trautinger, MD, Principal Investigator Susanne Eder, MD, Sub-Investigator
Department of Dermatology, Hospital Hietzing, Vienna A-1130, Austria; Not yet recruiting Paul-Gunther Sator, MD, Phone: +43 1 80110, Ext: 2422, Email: paul.sator@wienkav.at Andreas Steiner, MD, Phone: +43 1 80110, Ext: 2422 Andreas Steiner, MD, Principal Investigator Paul-Gunther Sator, MD, Sub-Investigator
Department of Dermatology, Medical University of Vienna, Vienna A-1090, Austria; Not yet recruiting Adrian Tanew, MD, Phone: +43 1 40400, Ext: 7710, Email: adrian.tanew@meduniwien.ac.at Anja Pinkowicz, MD, Phone: +43 1 40400, Ext: 7710 Adrian Tanew, MD, Principal Investigator Anja Pinkowicz, MD, Sub-Investigator
Department of Dermatology, Klinikum Wels, Wels A-4600, Austria; Not yet recruiting Werner Saxinger, MD, Phone: +43 7242 415, Ext: 9 2105, Email: werner.saxinger@klinikum-wegr.at Barbara Fleischanderl, MD, Phone: +43 7242 415, Ext: 9 2105 Werner Saxinger, MD, Principal Investigator Barbara Fleischanderl, MD, Sub-Investigator
Department of Dermatology, County Hospital Wiener Neustadt, Wiener Neustadt A-2700, Austria; Not yet recruiting Robert Muellegger, MD, Phone: +43 2622 321, Ext: 4901, Email: robert.muellegger@wienerneustadt.lknoe.at Nicolaus Sandor, MD, Phone: +43 2622 321, Ext: 4901 Robert Muellegger, MD, Principal Investigator Nicolaus Sandor, MD, Sub-Investigator
Additional Information
Starting date: February 2013
Last updated: June 3, 2015
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