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

TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides: a Prospective Randomized Controlled Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Mycosis Fungoides; Cutaneous T Cell Lymphoma
• Intervention / Treatment: Other: Low-dose total-skin electron-beam therapy; Other: Phototherapy

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Adèle DEMASSON; Phone Number: +33171 20 75 01; Email: adele.demasson@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Other: 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.
Other: 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.	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		at 5 years post inclusion
Proportion of patients with tumor clone eradication in skin	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	at 4 months after inclusion
Complete response rate	Complete response rate will be assessed using ISCL/EORTC criteria	at 4 months after inclusion
Overall response rates	Overall response rate will be assessed using ISCL/EORTC criteria	at 4 months after inclusion
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 5 years post inclusion
Quality of life as measured by the EORTC QLQ-C30	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.	at inclusion
Quality of life as measured by the EORTC QLQ-C30	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.	at 1 month
Quality of life as measured by the EORTC QLQ-C30	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.	at 4 months
Quality of life as measured by the EORTC QLQ-C30	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.	at 1 year
Quality of life as measured by the EORTC QLQ-C30	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.	at 2 years
Quality of life as measured by the EORTC QLQ-C30	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.	at 3 years
Quality of life as measured by the EORTC QLQ-C30	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.	at 4 years
Quality of life as measured by the EORTC QLQ-C30	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.	at 5 years
Quality of life as measured by the Skindex scale	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.	at inclusion
Quality of life as measured by the Skindex scale	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.	at 1 month
Quality of life as measured by the Skindex scale	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.	at 4 months
Quality of life as measured by the Skindex scale	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.	at 1 year
Quality of life as measured by the Skindex scale	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.	at 2 years
Quality of life as measured by the Skindex scale	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.	at 3 years
Quality of life as measured by the Skindex scale	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.	at 4 years
Quality of life as measured by the Skindex scale	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.	at 5 years
Proportion of patients with side effects	Evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	up to 5 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): February 1, 2027
• Study Completion (Anticipated): February 1, 2031

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma; Lymphoma, T-Cell; Mycoses; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides
• Other Study ID Numbers: APHP200128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No