Clinical trial NCT05205902: TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides
Official title: TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides: a Prospective Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Mycosis Fungoides
Cutaneous T Cell Lymphoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-01-25
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Progression free survival
timeFrame: at 12 months
Secondary outcomes:
measure: Proportion of patients with tumor clone eradication in skin
timeFrame: at 4 months after inclusion
measure: Complete response rate
timeFrame: at 4 months after inclusion
measure: Overall response rates
timeFrame: at 4 months after inclusion
measure: Progression-free survival
timeFrame: at 5 years post inclusion
measure: Overall survival
timeFrame: at 5 years post inclusion
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at inclusion
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 1 month
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 4 months
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 1 year
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 2 years
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 3 years
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 4 years
measure: Quality of life as measured by the EORTC QLQ-C30
timeFrame: at 5 years
measure: Quality of life as measured by the Skindex scale
timeFrame: at inclusion
measure: Quality of life as measured by the Skindex scale
timeFrame: at 1 month
measure: Quality of life as measured by the Skindex scale
timeFrame: at 4 months
measure: Quality of life as measured by the Skindex scale
timeFrame: at 1 year
measure: Quality of life as measured by the Skindex scale
timeFrame: at 2 years
measure: Quality of life as measured by the Skindex scale
timeFrame: at 3 years
measure: Quality of life as measured by the Skindex scale
timeFrame: at 4 years
measure: Quality of life as measured by the Skindex scale
timeFrame: at 5 years
measure: Proportion of patients with side effects
timeFrame: up to 5 years
Other outcomes:
Locations:
Study officials:
References: