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

NCT06651203 | Not Yet Recruiting

• 1 other identifier: APHP220915
• Study Type: observational
• Target: 460
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Specificity of KIR3DL2 in the diagnosis of Sezary syndrome

  Defined as the proportion of patients KIR3DL2 \<200/mm3 among patients without SS. Diagnosis of SS is defined as the presence of each of the following criteria: * T4 tumoral stage (erythrodermia ≥ 80% of total body area) * the presence of an identical T-cell clone evidenced in blood and skin * B2 blood stage Of note, according to ISCL/EORTC recommendations, FCM (Flow cytometry) blood staging is defined as: Stage B2: Expanded CD4+T cells with either CD4+CD26-≥30%, or CD4+CD7-≥40% And/or either CD4+CD7- or CD4+CD26-Tcells≥1000/mm3 Stage B1: Either CD4+CD7- or CD4+CD26-T-cells ≥250/mm3, but not meeting B2 criteria Stage B0: CD4+CD7- and CD4+CD26-T-cells\<250/mm3 Diagnosis and KIR3DL2 measurements will be performed using standardized/harmonized procedures across participating laboratories, using the same combination of labelled antibodies, gating strategies and instrument settings.

  At baseline, for group 1

Secondary Outcomes (14)

• Receiver Operating Characteristics (ROC) curve (Sensitivity, Specificity, area under the ROC curve) of KIR3DL2 in the diagnosis of SS and mycosis fungoides (MF) in eligible patients.

  At baseline, for group 1

• Positive and Negative predictive values of KIR3DL2 for SS diagnosis in the population of patients with clinical features consistent with erythrodermic CTCL

  Up to 24 months for group 1 patients

• Blood response

  At 3 months for group 1 and 2

• Blood response

  At 6 months for group 1 and 2

• Blood response

  At 9 months for group 1 and 2

Study Arms (2)

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

at initial diagnosis assessment

Other: Follow-up

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

Interventions

Follow-up OTHER

Clinical evaluation Blood sample Skin biopsy

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Patients with clinical features consistent with erythrodermic CTCL upon initial diagnosis assessment 2. Patients previously diagnosed with SS and followed at Saint-Louis hospital

You may qualify if:

• 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:
• Stage T4 erythroderma (stage (erythrodermia ≥ 80% of total body area)
• The presence of an identical T-cell clone evidenced in blood and skin
• B2 blood staging at initial diagnosis

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample, punch skin biopsy

MeSH Terms

Conditions

Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous

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

Central Study Contacts

Hélène Moins, MD PhD

CONTACT

142499629; helene.moins@u-paris.fr

Jérôme Lambert, MD PhD

CONTACT

142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: October 21, 2024

Record last verified: 2024-10