TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides
- Conditions
- Mycosis FungoidesCutaneous T Cell Lymphoma
- Interventions
- Other: Low-dose total-skin electron-beam therapyOther: Phototherapy
- Registration Number
- NCT05205902
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Primary cutaneous T-cell lymphomas are a group of peripheral T-cell lymphomas that primarily involve the skin. Mycosis fungoides (MF) is the most frequent subtype. Most patients with early-stage MF (i.e., patches and plaques of the skin without extracutaneous involvement) have a good prognosis but a subset of patients progress to incurable advanced-stage disease with an overall survival (OS) less than 5 years and an impaired quality of life.
We have recently identified the tumor clone frequency in lesional skin (measured by high-throughput sequencing of the TCRB locus) as the most important prognostic factor of progression-free survival (PFS) and OS in a retrospective analysis on 210 patients with early-stage MF (p\<0.001).
Phototherapy is a standard therapeutic option in early-stage MF but fails to eradicate the tumor clone from the skin.
Low-dose total-skin electron-beam therapy (LDTSEBT, 12 Gy over a 3-week period) has been shown to be safe and highly effective in MF with an 88% overall response rate and a better safety profile compared to standard-dose total-skin electron-beam therapy, in a pooled analysis from 3 phase II trials on 33 patients and a retrospective analysis of 12 patients treated with LDTSEBT.
We hypothesize that the use of LDTSEBT is associated with a significantly higher 1-year PFS compared to conventional treatment with phototherapy. Our secondary hypotheses are that LDTSEBT is associated with a higher tumor T-cell clone eradication compared to phototherapy, and improves OS and quality of life in patients with skin-limited MF.
The main objective of this study is therefore to prospectively determine if LDTSEBT is associated with a higher 1-year progression-free survival in patients with early-stage mycosis fungoides, compared to conventional treatment with phototherapy.
The primary endpoint is PFS at 12 months after study inclusion.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 78
- Age ≥ 18 years
- Histopathologically confirmed diagnosis of International Society for Cutaneous Lymphomas (ISCL) / European Organisation for Research and Treatment of Cancer (EORTC) mycosis fungoides stage IB or IIA
- Poor performance status: WHO performance status score > 2
- Physically unable to maintain the posture
- Patient with no health coverage
- Patient under guardianship or curatorship
- Previous history of dose-limiting radiation therapy in the field
- Previous history of dose-limiting phototherapy
- Previous history of melanoma, skin squamous cell carcinoma or basal cell carcinoma or other absolute contraindication to phototherapy (including a history of lupus, xeroderma pigmentosum, or porphyria)
- Pregnant or breastfeeding woman
- Contraindication to methoxsalen (severe liver, renal or heart failure)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low-dose total-skin electron-beam therapy Low-dose total-skin electron-beam therapy Low-dose total skin electron beam therapy (12 Gy) will be delivered to the patient in 4 Gy/week, 1 Gy/day over 3 weeks by symmetrical electron beams of 6 MeV energy via a linac accelerator. Phototherapy Phototherapy Phototherapy will be given 3 times a week during 2 months, then twice a week during one month, then once a week during one month, or until disease progression or unacceptable side effect, whatever comes first. Patients with plaques will receive PUVA therapy and patients with patches only will receive narrow-band UVB therapy.
- Primary Outcome Measures
Name Time Method Progression free survival at 12 months Progression will be defined clinically as \>25% increase in the modified Severity Weighted Assessment Tool (mSWAT) score from baseline or progression to advanced stage, according to the ISCL/EORTC criteria , or the onset of a new treatment of MF (excepted the use of topical corticosteroids, which is allowed during the study, and will not be considered as a new treatment
- Secondary Outcome Measures
Name Time Method Overall response rates at 4 months after inclusion Overall response rate will be assessed using ISCL/EORTC criteria
Quality of life as measured by the EORTC QLQ-C30 at 5 years Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Proportion of patients with side effects up to 5 years Evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Proportion of patients with tumor clone eradication in skin at 4 months after inclusion Tumor clone eradication in skin will be defined by \>90% reduction in the tumor cell content (tumor cells/100 ng DNA by high throughput sequencing of TCRB in a lesional skin biopsy) in skin
Complete response rate at 4 months after inclusion Complete response rate will be assessed using ISCL/EORTC criteria
Overall survival at 5 years post inclusion Progression-free survival at 5 years post inclusion Progression will be defined clinically as \>25% increase in the modified Severity Weighted Assessment Tool (mSWAT) score from baseline or progression to advanced stage, according to the ISCL/EORTC criteria , or the onset of a new treatment of MF (excepted the use of topical corticosteroids, which is allowed during the study, and will not be considered as a new treatment
Quality of life as measured by the Skindex scale at 5 years Quality of life will be measured by the Skindex scale-29 instruments which Measure the Effects of Skin Disease on Quality of Life The Skindex-29 scale is a three-dimensional,dermatology-specific health related quality of life (HRQL) questionnaire. thirty items are combined to form three domains: symptoms,emotions, and functioning. The overall score are expressed on a 100-point scale. A higher scores indicate lower level of quality of life.