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

NCT05205902 | Not Yet Recruiting Phase 3

• 1 other identifier: APHP200128
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Mycosis Fungoides; Cutaneous T Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  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

  at 12 months

Secondary Outcomes (22)

• Proportion of patients with tumor clone eradication in skin

  at 4 months after inclusion

• Complete response rate

  at 4 months after inclusion

• Overall response rates

  at 4 months after inclusion

• Progression-free survival

  at 5 years post inclusion

• Overall survival

  at 5 years post inclusion

Study Arms (2)

Low-dose total-skin electron-beam therapy

OTHER

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.

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

Phototherapy

OTHER

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.

Other: Phototherapy

Interventions

Low-dose total-skin electron-beam therapy OTHER

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.

Low-dose total-skin electron-beam therapy

Phototherapy OTHER

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.

Phototherapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous

Interventions

Phototherapy

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Adèle DEMASSON

CONTACT

+33171 20 75 01; adele.demasson@aphp.fr

Matthieu Resche-Rigon

CONTACT

+33142499742; matthieu.resche-rigon@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: January 25, 2022
• Study Start: February 1, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2031
• Last Updated: January 25, 2022

Record last verified: 2022-01