Evaluation of the KIR3DL2 Marker in Flow Cytometry for Sézary Syndrome Diagnosis, Therapeutic Response and Residual Disease: a Prospective and Multicenter Study

NCT ID: NCT06651203

Last Updated: 2024-10-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 460 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2029-11-01

Brief Summary

Cutaneous T-cell lymphomas (CTCL) are a group of primary cutaneous lymphomas including Mycosis Fungoides (MF) and Sézary syndrome (SS). SS is characterized by erythroderma and high numbers of circulating atypical lymphocytes (Sézary cells. SCs). Blood staging was added to the Tumor Node Metastasis (TNM) classification of MF/SS, reflecting the broad spectrum of CTCLs and the poor prognosis related to blood involvement. Blood classes were defined using blood-smear manual counts. However, this method never reached an international consensus status because of its subjective nature and its poor sensitivity. Several markers have been identified with variable efficiency for MF/SS diagnosis, outcome prediction and blood response to treatment. Such markers are essential for sharing and publishing consistent data about diagnosis, staging, prognosis and response to therapies. The detection of SCs is based on the lack of pan T-cell markers such as CD7 and/or CD26, which is not constant and may be observed in benign dermatoses. Thus, patients are often diagnosed with a delay, even treated with inappropriate therapies which worsens their prognosis. The relevance of blood-class in MF/SS is not only related to stage but also contributes to the response to therapy in clinical trials. We found that a significant proportion of benign T-cells from SS patients are CD4+CD26-, which may underestimate the rate of complete response to treatment. The identification of KIR3DL2 on SCs by our team has greatly helped the detailed study of the malignant clone. We have recently published two ancillary studies demonstrating the specificity and reliability of KIR3DL2 as a positive marker for SCs, and its prognosis value at initial diagnosis. We have designed an optimized flow-cytometry strategy as part of the routine care of erythrodermic patients at Saint-Louis Hospital and published in 2019 the results of a 5 years prospective single-center study involving 254 CTCL patients at initial diagnosis. We provided recommendations with the use a threshold value of KIR3DL2+SCs ≥ 200/µL or KIR3DL2+SCs/lymphocytes ≥ 10% in the diagnostic criteria and proposed a novel algorithm blood staging.

Several innovative immunotherapies in phase I/II trials or under compassionate use are ongoing in French centers, with the need to assess blood response using positive markers. Our goal is to validate KIR3DL2 as a specific marker for SS and to assess its reliability for blood staging and response to treatment in a multicenter study (11 centers).

Conditions

Mycosis Fungoides/Sezary Syndrome; Cutaneous T Cell Lymphoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with clinical features consistent with erythrodermic cutaneous T cell lymphoma (CTCL)

at initial diagnosis assessment

Follow-up

Intervention Type: OTHER

Clinical evaluation Blood sample Skin biopsy

Patients previously diagnosed with Sézary syndrome (SS) and followed at Saint-Louis hospital

No interventions assigned to this group

Interventions

Follow-up

Clinical evaluation Blood sample Skin biopsy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18
• Patients with health insurance
• Patients informed and not opposed to the study

• Patients with clinical features consistent with erythrodermic CTCL at initial diagnosis.

• Confirmed SS (previously diagnosed), followed at Saint Louis hospital participating center with all the following criteria:

1. Stage T4 erythroderma (stage (erythrodermia ≥ 80% of total body area)

2. The presence of an identical T-cell clone evidenced in blood and skin

3. B2 blood staging at initial diagnosis

Exclusion Criteria

• Other progressive neoplastic disease
• Progressive psychotic disease
• Patient under guardianship or curatorship
• Patients with state medical aid
• Refusal to participate

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Hélène Moins, MD PhD

Role: CONTACT

helene.moins@u-paris.fr

142499629 ext. +33

Jérôme Lambert, MD PhD

Role: CONTACT

jerome.lambert@u-paris.fr

142499742 ext. +33

Other Identifiers

APHP220915

Identifier Type: -

Identifier Source: org_study_id