Cutaneous T Cell Lymphoma, Mycosis Fungoides
Conditions
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.
Interventions
OTHERLow-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.
OTHERPhototherapy
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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | at 4 months after inclusion | Complete response rate will be assessed using ISCL/EORTC criteria |
| Overall response rates | at 4 months after inclusion | Overall response rate will be assessed using ISCL/EORTC criteria |
| 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 |
| 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 |
| Quality of life as measured by the EORTC QLQ-C30 | at inclusion | 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. |
| Quality of life as measured by the Skindex scale | at inclusion | 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 |
| Overall survival | at 5 years post inclusion | — |
Contacts
Primary ContactAdèle DEMASSON
Backup ContactMatthieu Resche-Rigon
Outcome results
None listed