TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides (TOTEM-01)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 3

Conditions: Cutaneous T Cell Lymphoma; Mycosis Fungoides

Treatments: Other: Low-dose total-skin electron-beam therapy; Other: Phototherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05205902

APHP200128

Details and patient eligibility

About

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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 2 patient groups

Low-dose total-skin electron-beam therapy

Other group

Description:

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.

Treatment:

Other: Low-dose total-skin electron-beam therapy

Phototherapy

Other group

Description:

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.

Treatment:

Other: Phototherapy