Mycosis Fungoides/Sezary SyndromeKISS01NCT06651203
Evaluation of the KIR3DL2 Marker in Flow Cytometry for Sézary Syndrome Diagnosis, Therapeutic Response and Residual Disease: a Prospective and Multicenter Study
An observational study of Mycosis Fungoides/Sezary Syndrome and Cutaneous T Cell Lymphoma, run by Assistance Publique - Hôpitaux de Paris.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mycosis Fungoides/Sezary Syndrome, Cutaneous T Cell Lymphoma
- What is being tested?
- Follow-up
- How many people
- 460 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2024to 1 Nov 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- Other progressive neoplastic disease
- Progressive psychotic disease
- Patient under guardianship or curatorship
- Patients with state medical aid
- Refusal to participate
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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).
- Being tested
- Follow-up
- Medical subject headings
- Mycosis Fungoides, Sezary Syndrome, Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follow-upOther
Clinical evaluation Blood sample Skin biopsy
| Study group | Role | What they receive |
|---|---|---|
| Patients with clinical features consistent with erythrodermic cutaneous T cell lymphoma (CTCL) | at initial diagnosis assessment Receives: Other: Follow-up | |
| Patients previously diagnosed with Sézary syndrome (SS) and followed at Saint-Louis hospital | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
The reference diagnosis of SS will be defined as in the primary endpoint. KIR3DL2 will be measured with by FCM. Sensitivity, Specificity and ROC curve will be estimated both with the absolute count of KIR3DL2 and with the percentage of KIR3DL2 within lymphocyte subset.
Measured: 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
Cut-off value used for KIR3DL2 : 200/mm3
Measured: Up to 24 months for group 1 patients
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 3 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 6 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 9 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 12 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 15 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 18 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 21 months for group 1 and 2
Blood response
Blood response using FCM and CD7 and CD26 markers as per latest ISCL and EORTC guidelines, with the definition of:
Complete response (CR) : B0 stage. Partial response (PR) : > 50% decrease in quantitative measurements of blood tumor burden from baseline in those with B2 stage at baseline.
Progressive disease (PD) : B0 to B2 or >50% increase from baseline and at least 5000 neoplastic cells/ mm3 or Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from nadir. Stable disease (SD) : Fails to attain criteria for CR, PR, or PD. Relapse : increase of neoplastic blood lymphocytes to ≥ B2 in those with CR.
Measured: At 24 months for group 1 and 2
Overall survival
Measured: Up to 24 months for group 1
Progression free survival
Measured: Up to 24 months for group 1
Minimal Residual Disease
Minimal Residual Disease (MRD) by multiparameter flow cytometric immunophenotyping and High Throughput Sequencing (HTS) based detection of clonal TCR gene rearrangements in patients with SS, at the time of CR remission, in comparison with baseline measurements on frozen PBMC.
Measured: At 24 months for group 1 and 2
Evolution to SS diagnosis as defined in the primary endpoint in stage B1 patients with KIR3DL2≥ 200/mm3 or ≥ 10% at baseline
Measured: Up to 24 months for group 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mycosis Fungoides/Sezary SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06651203
- Sponsor's protocol ID
- APHP220915
- Acronym
- KISS01
- Status last verified
- Oct 2024
- First submitted
- 18 Oct 2024
- Last updated
- 21 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the KIR3DL2 Marker in Flow Cytometry for Sézary Syndrome Diagnosis, Therapeutic Response and Residual Disease: a Prospective and Multicenter Study
- ClinicalTrials.gov ID
- NCT06651203
- Acronym / sponsor ID
- KISS01 / APHP220915
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 460 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 21 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with clinical features consistent with erythrodermic cutaneous T cell lymphoma (CTCL) | – | Other: Follow-upat initial diagnosis assessment |
| Patients previously diagnosed with Sézary syndrome (SS) and followed at Saint-Louis hospital | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (5 listed)
- Other progressive neoplastic disease
- Progressive psychotic disease
- Patient under guardianship or curatorship
- Patients with state medical aid
- Refusal to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Follow-upClinical evaluation Blood sample Skin biopsy | Other | Patients with clinical features consistent with erythrodermic cutaneous T cell lymphoma (CTCL) |
Primary outcome
Specificity of KIR3DL2 in the diagnosis of Sezary syndrome
Time frame: At baseline, for group 1
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.
14 secondary outcomes
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.
Time frame: 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
Time frame: Up to 24 months for group 1 patients
Blood response
Time frame: At 3 months for group 1 and 2
Blood response
Time frame: At 6 months for group 1 and 2
Blood response
Time frame: At 9 months for group 1 and 2
Blood response
Time frame: At 12 months for group 1 and 2
Blood response
Time frame: At 15 months for group 1 and 2
Blood response
Time frame: At 18 months for group 1 and 2
Blood response
Time frame: At 21 months for group 1 and 2
Blood response
Time frame: At 24 months for group 1 and 2
Overall survival
Time frame: Up to 24 months for group 1
Progression free survival
Time frame: Up to 24 months for group 1
Minimal Residual Disease
Time frame: At 24 months for group 1 and 2
Evolution to SS diagnosis as defined in the primary endpoint in stage B1 patients with KIR3DL2≥ 200/mm3 or ≥ 10% at baseline
Time frame: Up to 24 months for group 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Mycosis Fungoides/Sezary Syndrome
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome Patients
Mycosis Fungoides, Lymphomatoid Papulosis
Not yet recruitingPhase 2
Golidocitinib in Patients With Mycosis Fungoides/Sézary Syndrome and T-Cell Large Granular Lymphocytic Leukemia
Mycosis Fungoides/Sezary Syndrome, T-cell Large Granular Lymphocytic Leukemia
RecruitingObservational study
A Prospective, US-based Study Assessing Mogamulizumab-associated Rash in Patients Diagnosed With Mycosis Fungoides or Sezary Syndrome and Treated With Standard of Care Mogamulizumab
Recurrent Mycosis Fungoides, Recurrent Sezary Syndrome
Active, not recruitingPhase 1
Duvelisib and Nivolumab for the Treatment of Stage IIB-IVB Mycosis Fungoides and Sezary Syndrome
Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Mycosis Fungoides/Sezary Syndrome and Cutaneous T Cell Lymphoma, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hélène Moins, MD PhD (142499629 ext. +33, helene.moins@u-paris.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Specificity of KIR3DL2 in the diagnosis of Sezary syndrome (time frame: At baseline, for group 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024.