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PUVA Maintenance Therapy in Mycosis Fungoides (M_PUVA_2012)

Primary Purpose

Patch/Plaque Stage Mycosis Fungoides

Status
Completed
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
8-methoxypsoralen
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patch/Plaque Stage Mycosis Fungoides focused on measuring Mycosis fungoides, Psoralen and UVA (PUVA), Photochemotherapy, Maintenance treatment, Immune function

Eligibility Criteria

18 Years - 82 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medical University of Graz
  • Department of Dermatology, Medical University of Innsbruck
  • Department of Dermatology, General Hospital of the City of Linz
  • Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University
  • Department of Dermatology, County Hospital St. Pölten
  • Department of Dermatology, Medical University of Vienna
  • Department of Dermatology, Hospital Hietzing
  • Department of Dermatology, Klinikum Wels
  • Department of Dermatology, County Hospital Wiener Neustadt

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

PUVA maintenance treatment

No maintenance treatment

Arm Description

Psoralen plus UVA (PUVA) treatment. The patients receive a standardized dose of oral 8-methoxypsoralen (Oxsoralen) 1 hour before UVA exposure

observation

Outcomes

Primary Outcome Measures

Recurrence after complete remission within 12 months post therapy
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
Compared to baseline
HADS
Hospital anxiety depression score, compared to baseline;
Cytokine response in serum
Compared to baseline
Levels of regulatory T cells
Compared to baseline
Function of regulatory T cells
Compared to baseline
Microscopic alterations
Quantification of histologic response in skin biopsy
Cytokine expression in the skin
Rt-PCR and immunohistochemical staining investigations

Full Information

First Posted
May 9, 2012
Last Updated
November 12, 2018
Sponsor
Medical University of Graz
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1. Study Identification

Unique Protocol Identification Number
NCT01686594
Brief Title
PUVA Maintenance Therapy in Mycosis Fungoides
Acronym
M_PUVA_2012
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 Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
July 2, 2018 (Actual)
Study Completion Date
July 2, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Graz

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patch/Plaque Stage Mycosis Fungoides
Keywords
Mycosis fungoides, Psoralen and UVA (PUVA), Photochemotherapy, Maintenance treatment, Immune function

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PUVA maintenance treatment
Arm Type
Active Comparator
Arm Description
Psoralen plus UVA (PUVA) treatment. The patients receive a standardized dose of oral 8-methoxypsoralen (Oxsoralen) 1 hour before UVA exposure
Arm Title
No maintenance treatment
Arm Type
No Intervention
Arm Description
observation
Intervention Type
Drug
Intervention Name(s)
8-methoxypsoralen
Other Intervention Name(s)
Oxsoralen®; Gerot Pharmazeutika GmbH, Vienna, Austria
Intervention Description
8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure
Primary Outcome Measure Information:
Title
Recurrence after complete remission within 12 months post therapy
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.
Time Frame
12 months after end of therapy
Secondary Outcome Measure Information:
Title
Quality of life
Description
Compared to baseline
Time Frame
Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
Title
HADS
Description
Hospital anxiety depression score, compared to baseline;
Time Frame
Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
Title
Cytokine response in serum
Description
Compared to baseline
Time Frame
Week -4 to 0; week 6, 12, 24, and 48
Title
Levels of regulatory T cells
Description
Compared to baseline
Time Frame
Week -4 to 0; week 6, 12, 24, and 48
Title
Function of regulatory T cells
Description
Compared to baseline
Time Frame
Week -4 to 0; week 6, 12, 24, and 48
Title
Microscopic alterations
Description
Quantification of histologic response in skin biopsy
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
Title
Cytokine expression in the skin
Description
Rt-PCR and immunohistochemical staining investigations
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
82 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Wolf, MD
Organizational Affiliation
Medical University of Graz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz
City
Graz
ZIP/Postal Code
8010
Country
Austria
Facility Name
Department of Dermatology, Medical University of Innsbruck
City
Innsbruck
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Department of Dermatology, General Hospital of the City of Linz
City
Linz
ZIP/Postal Code
A-4021
Country
Austria
Facility Name
Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University
City
Salzburg
ZIP/Postal Code
A-5020
Country
Austria
Facility Name
Department of Dermatology, County Hospital St. Pölten
City
St. Pölten
ZIP/Postal Code
A-3100
Country
Austria
Facility Name
Department of Dermatology, Medical University of Vienna
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Department of Dermatology, Hospital Hietzing
City
Vienna
ZIP/Postal Code
A-1130
Country
Austria
Facility Name
Department of Dermatology, Klinikum Wels
City
Wels
ZIP/Postal Code
A-4600
Country
Austria
Facility Name
Department of Dermatology, County Hospital Wiener Neustadt
City
Wiener Neustadt
ZIP/Postal Code
A-2700
Country
Austria

12. IPD Sharing Statement

Citations:
PubMed Identifier
32850876
Citation
Graier T, Fink-Puches R, Porkert S, Lang R, Pochlauer S, Ratzinger G, Tanew A, Selhofer S, Sator PG, Hofer A, Gruber-Wackernagel A, Legat FJ, Vieyra-Garcia PA, Quehenberger F, Wolf P. Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it. Front Med (Lausanne). 2020 Aug 5;7:330. doi: 10.3389/fmed.2020.00330. eCollection 2020.
Results Reference
derived
PubMed Identifier
30892603
Citation
Vieyra-Garcia P, Fink-Puches R, Porkert S, Lang R, Pochlauer S, Ratzinger G, Tanew A, Selhofer S, Paul-Gunther S, Hofer A, Gruber-Wackernagel A, Legat F, Patra V, Quehenberger F, Cerroni L, Clark R, Wolf P. Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial. JAMA Dermatol. 2019 May 1;155(5):538-547. doi: 10.1001/jamadermatol.2018.5905. Erratum In: JAMA Dermatol. 2019 May 1;155(5):638. JAMA Dermatol. 2019 Oct 1;155(10):1201. Abstract corrected.
Results Reference
derived

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PUVA Maintenance Therapy in Mycosis Fungoides

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