Clinical trial NCT06651203: Evaluation of the KIR3DL2 Marker in Flow Cytometry for Sézary Syndrome Diagnosis, Therapeutic Response and Residual Disease: a Prospective and Multicenter Study
Official title: Evaluation of the KIR3DL2 Marker in Flow Cytometry for Sézary Syndrome Diagnosis, Therapeutic Response and Residual Disease: a Prospective and Multicenter Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Mycosis Fungoides/Sezary Syndrome
Cutaneous T Cell Lymphoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-10-21
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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).


Eligibility criteria: Inclusion criteria for all patient :

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

Inclusion criteria for group 1 :

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

Inclusion criteria for group 2 :

* 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

Primary outcomes:
measure: Specificity of KIR3DL2 in the diagnosis of Sezary syndrome
timeFrame: At baseline, for group 1
Secondary outcomes:
measure: 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.
timeFrame: At baseline, for group 1
measure: Positive and Negative predictive values of KIR3DL2 for SS diagnosis in the population of patients with clinical features consistent with erythrodermic CTCL
timeFrame: Up to 24 months for group 1 patients
measure: Blood response
timeFrame: At 3 months for group 1 and 2
measure: Blood response
timeFrame: At 6 months for group 1 and 2
measure: Blood response
timeFrame: At 9 months for group 1 and 2
measure: Blood response
timeFrame: At 12 months for group 1 and 2
measure: Blood response
timeFrame: At 15 months for group 1 and 2
measure: Blood response
timeFrame: At 18 months for group 1 and 2
measure: Blood response
timeFrame: At 21 months for group 1 and 2
measure: Blood response
timeFrame: At 24 months for group 1 and 2
measure: Overall survival
timeFrame: Up to 24 months for group 1
measure: Progression free survival
timeFrame: Up to 24 months for group 1
measure: Minimal Residual Disease
timeFrame: At 24 months for group 1 and 2
measure: Evolution to SS diagnosis as defined in the primary endpoint in stage B1 patients with KIR3DL2≥ 200/mm3 or ≥ 10% at baseline
timeFrame: Up to 24 months for group 1
Other outcomes:
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