Deep Phenotyping of Cutaneous T Cell Lymphoma, Type Mycosis Fungoides

NCT05303480 | Completed

• 3 other identifiers: CHDR19472021-001576-41NL77292.056.21
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Mycosis fungoides (MF) is an ultra-orphan disease of which the etiology remains unknown. MF is diagnosed by correlating clinical appearance with histopathological analysis of often multiple invasive skin punch biopsies. To move patient care and the development of novel treatments for MF forward, objective, sensitive and reliable tools that are preferably non-invasive are desired. Therefore, the objective of the current study is to phenotype the early stages of mycosis fungoides in detail and to assess the response of chlormethine (CL) gel monotherapy. With this approach the investigators aim to detect novel biomarkers and to establish methodologies for the (non-)invasive monitoring of MF.

Conditions

Mycosis Fungoides

Keywords

Mycosis Fungoides; Cutaneous T Cell Lymphoma; Biomarker; Chlormethine; Ledaga

Outcome Measures

Primary Outcomes (28)

• Composite Assessment of Index Lesions Disease Severity Score (CAILS)

  CAILS is a composite score to quantify lesion severity and consists of scoring erythema, hypo-/hyperpigmentation, plaque elevation, desquamation and lesion size. The CAILS score of a single lesion ranges from 0 (unaffected) to 50 (severely affected).

  from day -42 to day 155

• Modified Severity Weighted Assessment Tool (mSWAT)

  mSWAT combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 (unaffected) to 400 (severely affected).

  from day -42 to day 155

• Objective Response Rate (ORR)

  The Objective Response Rate (ORR) measures the lesional response as the change from baseline for the CAILS and mSWAT score. The ORR is the number of patients with complete response (100% clearance) + the number of patients with partial response (50%-99%) divided by the total number of patients.

  from day 43 to day 155

• SKINDEX-29: Quality of life (QoL)

  The Skindex-29 is a valid 29-item self-report measure that evaluates health-related QoL for patients with dermatological diseases. The score is subdivided in a domain for symptoms, emotions and fuctioning; domain scores range from 0 (no impact) to 100 (severely impacted). Total Skindex-29 score is calculated as a mean of the three domains, ranging from 0 (no impact on QoL) to 100 (QoL severely impacted).

  from day 0 to day 155

• Treatment Satisfaction Questionnaire for Medication (TSQM)

  TSQM consists of 14 questions and explores the subject satisfaction regarding the effectiveness, the side effects, convenience and global satisfaction of the investigational drug. The TSQM score ranges from 0 (lowest satisfaction) to 100 (highest satisfaction).

  from day 43 to day 155

• Patient reported outcomes

  Patients will be asked to report on their condition through a Numerical Rating Scale (0 (better)- 100 (worse)) for itch, pain and sleeplessness.

  from day 0 to day 155

• Erythema measurement of the skin

  Redness of the skin will be determined using a colorimeter

  from day 0 to day 155

• 3D Multispectral imaging

  The redness and superficial morphology of (non-)lesional skin sites will be determined using a 3D multispectral imaging system.

  from day 0 to day 155

• Laser Speckle Contrast Imaging (LSCI)

  The cutaneous microcirculation of (non-)lesional skin sites will be monitored over a 40 second timespan with a laser speckle contrast imager.

  from day 0 to day 155

• Thermography

  Body surface temperature of (non-)lesional skin will be determined using a thermal imaging infrared camera.

  from day 0 to day 155

• Optical Coherence Tomography (OCT)

  OCT is a non-invasive assessment which visualizes skin morphology in vivo to a depth of 2 mm with the use of infrared light.

  from day 0 to day 155

• Skin barrier function by Trans-Epidermal Water Loss (TEWL)

  The barrier status by trans epidermal water loss of (non-)lesional skin will be determined using TEWL. (g/m2/h)

  from day 0 to day 155

• Cutaneous microbiome

  The cutaneous microbiome of (non-)lesional skin is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.

  from day 0 to day 155

• Faecal microbiome

  The bacterial composition of stool samples pre- and post-treatment will be determined using next-generation sequencing.

  from day 43 to day 155

• Skin surface biomarkers

  Superficial protein biomarkers of (non-)lesional skin will be assessed by a non-invasive transdermal patch by FibroTx. The presence of protein biomarkers will be determined using ELISA. The following biomarkers will be assessed (ng/ul): IL-8, CXCL-2, IL-1A, IL-1RA, CCL-17 and CCL-27 and VEGF.

  from day 0 to day 155

• Lipidomics of the stratum corneum by liquid chromatography mass spectroscopy

  Tape stripping will be performed on (non-)lesional skin and lipids are subsequently extracted from the tape and analyzed using Liquid Chromatography-Mass Spectrometry (ng/cm2).

  from day 0 to day 155

• Patient genotyping

  A whole blood sample will be used to scan for common mutations in genes implicated in mycosis fungoides using next-generation sequencing.

  day 43

• Blister immune cell subsets

  Blisters will be induced on the (non-)lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry.

  day 43

• Blister protein biomarkers by high-throughput, multiplex immunoassays of proteins by Proximity Estension Assay (PEA) technology

  Blisters will be induced on the (non-)lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines using the Olink inflammation and immuno-oncology panel (96 proteins per panel, e.g. PD-L1, IL-4, IL-12, IL-13, ng/ml).

  day 43

• Immunohistochemistry and Imaging Mass Cytometry/VECTRA of biopsies

  Biopsies will be sectioned and stained for the determination of the cutaneous homeostasis and tumor micro-environment by visualising infiltration of cellular immune subsets (e.g. presence of CD4 and CD8).

  from day 43 to day 155

• Circulating protein biomarkers by PCR amplification

  Blood will be drawn using a venipuncture during visits and analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8).

  from day 0 to day 155

• Cells/ml; Circulating immune cell subsets

  Blood will be drawn using a venipuncture during visits and analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry.

  from day 0 to day 155

• Itch Tracking by Derma Track

  Subjects are requested to wear a smartwatch during the night to register total duration of scratch movements.

  from day 0 to day 155

• User experience and subjective burden questionnaire

  Measures the user experience and subjective burden of the different imaging modalities used in this study. Scores ranging from 0 (no burden) to 100 (severe burden).

  from day 43 to day 155

• Blister immune cell subsets during dermatitis reactions

  Blisters will be induced on the lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry.

  from day 43 to day 155

• Change from baseline in blister immune cell subsets after 16 weeks of treatment

  Blisters will be induced on the lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry.

  day 43 and day 155

• Blister protein biomarkers by high-throughput, multiplex immunoassays of proteins by Proximity Estension Assay (PEA) technology

  Blisters will be induced on the lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines using the Olink inflammation and immuno-oncology panel (96 proteins per panel, e.g. PD-L1, IL-4, IL-12, IL-13, ng/ml).

  from day 43 to day 155

• Change from baseline in blister protein biomarkers, by high-throughput, multiplex immunoassays of proteins by Proximity Estension Assay (PEA) technology

  Blisters will be induced on the lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines using the Olink inflammation and immuno-oncology panel (96 proteins per panel, e.g. PD-L1, IL-4, IL-12, IL-13, ng/ml).

  day 43 and day 155

Study Arms (2)

Chlormethine gel

ACTIVE COMPARATOR

Chlormethine gel 0.016% in 60mg tube, topical home administration from day 0 to day 155.

Drug: Chlormethine

Healthy volunteers

NO INTERVENTION

Healthy volunteer cohort (observational)

Interventions

Chlormethine DRUG

Chlormethine gel 0.016%

Also known as: Ledaga, Valchlor

Chlormethine gel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure;
• Male or female subjects, 18 to 75 years of age, inclusive at screening; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigators;
• Body mass index (BMI) ≥ 18.0 and ≤ 40.0 kg/m2; during COVID-19 pandemic only ≥ 18.0 and ≤ 33.0 kg/m2;
• No clinically significant skin disease as judged by the investigator;
• No history of hypertrophic scarring or keloid;
• Subject is willing to refrain from extensively washing (including bathing, swimming, showering and excessive sweating) the skin 4 hours before every study visit;
• Subject is willing and able to washout and withhold any topical treatment (prescription and over the counter products) in the treatment area (if possible matched location to most common location of target lesions of the MF group, and otherwise 100cm2 on the lower back) for 2 weeks prior to Day 1;
• Subject is willing to refrain from application of any topical product (e.g. ointments, crème or washing lotions) on the skin 24 hours prior to every study visit day;
• Subject is willing and able to washout (topical and oral) antibiotic therapy for 14 days prior to Day 1;
• Subject is willing to use effective contraception from screening until EOS if subject is male or women of childbearing potential;
• Subject has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements.
• Signed informed consent prior to any study-mandated procedure;
• Male or female subjects, 18 to 75 years of age, inclusive at screening; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigators
• Body mass index (BMI) ≥ 18.0 and ≤ 40.0 kg/m2; during COVID-19 pandemic only ≥ 18.0 and ≤ 33.0 kg/m2;
• At least one patch and/or plaque lesion present, with at least one dimension with a diameter of ≥ 6cm;

You may not qualify if:

• History of immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator;
• The use of systemic antibiotic therapy for \>2 months the past 12 months;
• The use of any oral/systemic medication (e.g. immunomodulatory, immunosuppressive) within 28 days prior to Day 1, if the investigator judges that it may interfere with the study objectives.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIV ab) at screening;
• Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year;
• Loss or donation of blood over 500mL within three months prior to screening;
• History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months of screening. Alcohol consumption will be prohibited from at least 24 hours preceding each study visit;
• Positive urine test for drugs or history of abuse at screening or pre-dose. Urine drug test may be repeated at the discretion of the investigator;
• Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding;
• Any other known factor, condition, or disease that might interfere with study conduct or interpretation.
• Have any current relevant skin infections/disease in the treatment area other than the observational disease (mycosis fungoides), inclusively, but not limited to atopic dermatitis, psoriasis vulgaris, dermatomycosis and other skin malignancies.
• Having received treatments for MF or any other disease within the following intervals prior to the start of the study (The use of topical emollients is allowed during the study. For target lesions it is allowed up to 24h before every study visit day):
• \< 2 weeks for topical treatment, e.g. corticosteroids, retinoids, vitamin D analogs
• \<4 weeks for phototherapy, e.g. UVB, PUVA, PDT
• \<4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate

Sponsors & Collaborators

• Centre for Human Drug Research, Netherlands: lead
• RECORDATI GROUP: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

MeSH Terms

Conditions

Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous

Interventions

Mechlorethamine; Amines

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

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Officials

• Robert Rissmann, Prof. Dr.

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an observational and interventional study in 20 Mycosis Fungoides patients and 10 healthy volunteers (observational only).

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: March 31, 2022
• Study Start: December 7, 2021
• Primary Completion: December 8, 2022
• Study Completion: December 8, 2022
• Last Updated: January 25, 2023

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)