TOTEM-01: TOtal Skin Electron Beam Therapy (Low-dose) for Tumor Clone Eradication in Early-stage Mycosis Fungoides
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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
- Overall survival [at 5 years post inclusion]
- 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 EORTC QLQ-C30 [at 1 month]
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 EORTC QLQ-C30 [at 4 months]
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 EORTC QLQ-C30 [at 1 year]
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 EORTC QLQ-C30 [at 2 years]
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 EORTC QLQ-C30 [at 3 years]
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 EORTC QLQ-C30 [at 4 years]
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 EORTC QLQ-C30 [at 5 years]
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.
- Quality of life as measured by the Skindex scale [at 1 month]
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.
- Quality of life as measured by the Skindex scale [at 4 months]
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.
- Quality of life as measured by the Skindex scale [at 1 year]
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.
- Quality of life as measured by the Skindex scale [at 2 years]
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.
- Quality of life as measured by the Skindex scale [at 3 years]
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.
- Quality of life as measured by the Skindex scale [at 4 years]
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.
- Quality of life as measured by the Skindex scale [at 5 years]
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.
- Proportion of patients with side effects [up to 5 years]
Evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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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:
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Poor performance status: WHO performance status score > 2
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Physically unable to maintain the posture
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Patient with no health coverage
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Patient under guardianship or curatorship
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Previous history of dose-limiting radiation therapy in the field
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Previous history of dose-limiting phototherapy
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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)
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Pregnant or breastfeeding woman
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Contraindication to methoxsalen (severe liver, renal or heart failure)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP200128