PUVA Maintenance Therapy in Mycosis Fungoides (M_PUVA_2012)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Medical University of Graz
Sponsor:
Information provided by (Responsible Party):
Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01686594
First received: May 9, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Patch/Plaque Stage Mycosis Fungoides
Drug: 8-methoxypsoralen
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Recurrence after complete remission within 12 months post therapy [ Time Frame: 12 months after end of therapy ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Quality of life [ Time Frame: Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72 ] [ Designated as safety issue: No ]
    Compared to baseline

  • HADS [ Time Frame: Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72 ] [ Designated as safety issue: No ]
    Hospital anxiety depression score, compared to baseline;

  • Cytokine response in serum [ Time Frame: Week -4 to 0; week 6, 12, 24, and 48 ] [ Designated as safety issue: No ]
    Compared to baseline

  • Levels of regulatory T cells [ Time Frame: Week -4 to 0; week 6, 12, 24, and 48 ] [ Designated as safety issue: No ]
    Compared to baseline

  • Function of regulatory T cells [ Time Frame: Week -4 to 0; week 6, 12, 24, and 48 ] [ Designated as safety issue: No ]
    Compared to baseline

  • Microscopic alterations [ Time Frame: Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5 ] [ Designated as safety issue: No ]
    Quantification of histologic response in skin biopsy

  • Cytokine expression in the skin [ Time Frame: Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5 ] [ Designated as safety issue: No ]
    Rt-PCR and immunohistochemical staining investigations


Estimated Enrollment: 82
Study Start Date: February 2013
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PUVA maintenance treatment
Psoralen plus UVA (PUVA) treatment. The patients receive a standardized dose of oral 8-methoxypsoralen (Oxsoralen) 1 hour before UVA exposure
Drug: 8-methoxypsoralen
8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure
Other Name: Oxsoralen®; Gerot Pharmazeutika GmbH, Vienna, Austria
No Intervention: No maintenance treatment
observation

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

Ages Eligible for Study:   18 Years to 82 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686594

Contacts
Contact: Peter Wolf, MD +43 316 385 ext 80315 peter.wolf@medunigraz.at
Contact: Regina Fink-Puches, MD+ +43 316 385 ext 80428 regina.fink@medunigraz.at

Locations
Austria
Medical University of Graz Recruiting
Graz, Austria, 8010
Contact: Peter Wolf, MD    +43 316 385 ext 80315    peter.wolf@medunigraz.at   
Contact: Regina Fink-Puches, MD    +43 316 385 ext 12371    regina.fink@medunigraz.at   
Principal Investigator: Peter Wolf, MD         
Sub-Investigator: Regina Fink-Puches, MD         
Department of Dermatology, Medical University of Innsbruck Not yet recruiting
Innsbruck, Austria, A-6020
Contact: Gudrun Ratzinger, MD    +43 512 504 ext 81484    gudrun.ratzinger@i-med.ac.at   
Contact: Matthias Schmuth, MD    +43 512 504      
Principal Investigator: Matthias Schmuth, MD         
Sub-Investigator: Gudrun Ratzinger, MD         
Department of Dermatology, General Hospital of the City of Linz Not yet recruiting
Linz, Austria, A-4021
Contact: Josef Auböck, MD    +43 732 7806 ext 3732    josef.auboeck@akh.linz.at   
Contact: Christine Scheurecker, MD    +43 732 7806 ext 3732    christine.scheurecker@akh.linz.at   
Principal Investigator: Josef Auböck, MD         
Sub-Investigator: Christine Scheurecker, MD         
Sub-Investigator: Susanne Gross, MD         
Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University Not yet recruiting
Salzburg, Austria, A-5020
Contact: Helmut Hintner, MD    +43 662 4482 ext 3001    h.hintner@salk.at   
Contact: Sylvia Selhofer, MD    +43 662 4482 ext 3001    S.Selhofer@salk.at   
Principal Investigator: Helmut Hintner, MD         
Sub-Investigator: Sylvia Selhofer, MD         
Department of Dermatology, County Hospital St. Pölten Not yet recruiting
St. Pölten, Austria, A-3100
Contact: Franz Trautinger, MD    +43 2742 300 ext 11906    franz.trautinger@meduniwien.ac.at   
Contact: Susanne Eder, MD    +43 2742 300 ext 11906      
Principal Investigator: Franz Trautinger, MD         
Sub-Investigator: Susanne Eder, MD         
Department of Dermatology, Hospital Hietzing Not yet recruiting
Vienna, Austria, A-1130
Contact: Paul-Gunther Sator, MD    +43 1 80110 ext 2422    paul.sator@wienkav.at   
Contact: Andreas Steiner, MD    +43 1 80110 ext 2422      
Principal Investigator: Andreas Steiner, MD         
Sub-Investigator: Paul-Gunther Sator, MD         
Department of Dermatology, Medical University of Vienna Not yet recruiting
Vienna, Austria, A-1090
Contact: Adrian Tanew, MD    +43 1 40400 ext 7710    adrian.tanew@meduniwien.ac.at   
Contact: Anja Pinkowicz, MD    +43 1 40400 ext 7710      
Principal Investigator: Adrian Tanew, MD         
Sub-Investigator: Anja Pinkowicz, MD         
Department of Dermatology, Klinikum Wels Not yet recruiting
Wels, Austria, A-4600
Contact: Werner Saxinger, MD    +43 7242 415 ext 9 2105    werner.saxinger@klinikum-wegr.at   
Contact: Barbara Fleischanderl, MD    +43 7242 415 ext 9 2105      
Principal Investigator: Werner Saxinger, MD         
Sub-Investigator: Barbara Fleischanderl, MD         
Department of Dermatology, County Hospital Wiener Neustadt Not yet recruiting
Wiener Neustadt, Austria, A-2700
Contact: Robert Muellegger, MD    +43 2622 321 ext 4901    robert.muellegger@wienerneustadt.lknoe.at   
Contact: Nicolaus Sandor, MD    +43 2622 321 ext 4901      
Principal Investigator: Robert Muellegger, MD         
Sub-Investigator: Nicolaus Sandor, MD         
Sponsors and Collaborators
Medical University of Graz
Investigators
Principal Investigator: Peter Wolf, MD Medical University of Graz
  More Information

No publications provided

Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT01686594     History of Changes
Other Study ID Numbers: EudraCT 2012-000212-28, 24-169 ex 11/12
Study First Received: May 9, 2012
Last Updated: July 22, 2014
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by Medical University of Graz:
Mycosis fungoides
Psoralen and UVA (PUVA)
Photochemotherapy
Maintenance treatment
Immune function

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methoxsalen
Photosensitizing Agents
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 16, 2014