- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01686594
PUVA Maintenance Therapy in Mycosis Fungoides (M_PUVA_2012)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Graz, Austria, 8010
- Medical University of Graz
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Innsbruck, Austria, A-6020
- Department of Dermatology, Medical University of Innsbruck
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Linz, Austria, A-4021
- Department of Dermatology, General Hospital of the City of Linz
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Salzburg, Austria, A-5020
- Department of Dermatology, Hospital Salzburg - Paracelsus Private Medical University
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St. Pölten, Austria, A-3100
- Department of Dermatology, County Hospital St. Pölten
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Vienna, Austria, A-1090
- Department of Dermatology, Medical University of Vienna
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Vienna, Austria, A-1130
- Department of Dermatology, Hospital Hietzing
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Wels, Austria, A-4600
- Department of Dermatology, Klinikum Wels
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Wiener Neustadt, Austria, A-2700
- Department of Dermatology, County Hospital Wiener Neustadt
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
8-methoxypsoralen 10mg per 20 kg body weight 1 hour before UVA exposure
Other Names:
|
No Intervention: No maintenance treatment
observation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recurrence after complete remission within 12 months post therapy
Time Frame: 12 months after end of 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. |
12 months after end of therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Compared to baseline
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Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
|
HADS
Time Frame: Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
|
Hospital anxiety depression score, compared to baseline;
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Week -4 to 0; week 12, 24, 36, and 48; month 15, 18, 21, 24, 36, 48, 60, and 72
|
Cytokine response in serum
Time Frame: Week -4 to 0; week 6, 12, 24, and 48
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Compared to baseline
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Week -4 to 0; week 6, 12, 24, and 48
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Levels of regulatory T cells
Time Frame: Week -4 to 0; week 6, 12, 24, and 48
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Compared to baseline
|
Week -4 to 0; week 6, 12, 24, and 48
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Function of regulatory T cells
Time Frame: Week -4 to 0; week 6, 12, 24, and 48
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Compared to baseline
|
Week -4 to 0; week 6, 12, 24, and 48
|
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
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Quantification of histologic response in skin biopsy
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Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5
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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
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Rt-PCR and immunohistochemical staining investigations
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Week -4 to 0; and week 6; optional at week 12, 24, and 48; and in the follow-up from year 1 to 5
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Peter Wolf, MD, Medical University of Graz
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Bacterial Infections and Mycoses
- Lymphoma
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, T-Cell
- Mycoses
- Mycosis Fungoides
- Photosensitizing Agents
- Dermatologic Agents
- Methoxsalen
Other Study ID Numbers
- EudraCT 2012-000212-28
- 24-169 ex 11/12 (Other Identifier: Ethics committee Medical University of Graz)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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