Primary- To evaluate disease-related characteristics and biomarkers in patients with mycosis fungoides compared to healthy volunteers; Secondary- To evaluate the variability of the selected biomarkers between patients and within patients over time…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This study will monitor the changes over time of selected biomarkers. For
clinical applicability, a biomarker should be comparable over time and
distinctive within the selected study groups (healthy/MF-patients and
lesional/non-lesional). Due to the exploratory nature of this study, a major
primary endpoint is missing. Furthermore, based on developments in analysis or
based on results, additional analysis on the taken samples could be added in
the future. The following general endpoints have been defined, with the groups
defined as early-stage MF-patients and healthy volunteers.
* Comparable biomarker measurements (as described below under endpoints) over
time and within groups for the observational part of the study
* Difference in non-invasive and/or invasive biomarker measurements between
different groups (that ultimately could lead to improved disease classification)
* MF subgroups (responders vs non-responders): change in any of the invasive
and/or non-invasive biomarkers after 16 weeks of treatment with CL gel compared
to measurements of untreated/non-lesional skin
Secondary outcome
N.v.t.
Background summary
In recent years, knowledge about the wide spectrum of cutaneous T-cell
lymphomas (CTCL) has broadened. Mycosis fungoides (MF) comprises about 50-70%
of all primary cutaneous T-cell lymphomas (Willemze et al, 2019). Many CTCL are
misdiagnosed due to clinical and histopathological similarity to other skin
conditions (such as psoriasis vulgaris, atopic dermatitis and tinea corpora),
low prevalence of disease and a lack of reliable tools for detection of these
diseases, resulting in delayed diagnosis with years of discomfort and possibly
a worse prognosis. Furthermore, standard treatment has never been proven
curative, has many side effects and exacerbations are frequent. To date, the
etiology of mycosis fungoides remains unknown and little research has been
conducted into the mechanisms underlying its development and its response to
treatment.
Mycosis fungoides lesions change over time and differ between patients,
consisting of three morphologically different stages: patches
(erythematosquamous maculae), plaques (erythematosquamous, elevated and
occasionally infiltrated lesions) and tumors (with or without ulceration). Only
a relatively small group of patients advances to tumor stage MF during their
lifetime. Mycosis fungoides is diagnosed by correlating clinical appearance
with histopathological analysis of an invasive skin punch biopsy. Additionally,
often multiple biopsies are required after diagnosis, e.g. when a lesion is
clinically advancing to a different stage or if lesion origin is ambiguous.
Currently no other biomarkers besides skin punch biopsies markers are available
for the diagnosis of MF, the evaluation of a MF lesion over time, and the
monitoring of a potential treatment effect. To advance MF patient care and the
development of novel treatments for MF objective, sensitive and reliable
(preferably non-invasive) tools are desired.
Therefore, the objective of the current study is to phenotype the early stages
of mycosis fungoides in detail and to assess chlormethine (CL) gel monotherapy.
With this approach we aim to detect novel biomarkers and to establish
methodologies for the (non-)invasive monitoring of MF.
Study objective
Primary
- To evaluate disease-related characteristics and biomarkers in patients with
mycosis fungoides compared to healthy volunteers;
Secondary
- To evaluate the variability of the selected biomarkers between patients and
within patients over time.
- To evaluate biomarkers for disease-monitoring following CL gel treatment
- To investigate and monitor skin-related AEs that might develop after CL gel
application in MF patients
Study design
This is a single-center, two-part, combined observational and interventional
study.
Intervention
Chlormethine gel 0.016%, thrice weekly the first 4 weeks followed by once daily
for the next 12 weeks
Study burden and risks
The overall aim of this study is to evaluate objectively measured disease
related characteristics to comprehensively characterize patients with mycosis
fungoides compared to healthy volunteers.
Benefit
No medical benefit can be expected during the observational part of this study
for the participating subjects. For MF-patients continuing in the
interventional part, partial to complete mSWAT response may be expected for
63.3% of the patients after 12 months of treatment (including the optional
extension protocol). Partial to complete response by CAILS may be expected for
approximately 25% of the patients after 16 weeks of treatment and for 76.7%
after CL gel treatment for 12 months (Lessin et al., 2013). It is important to
note that in case of partial response patient can continue CL treatment after
EOS in an outpatient setting.
Risks
Albeit all study procedures are considered minimal invasive, participants can
experience pain and/or haematoma and in rare cases local infection during and
after a punch biopsy and/or venepuncture. Both biopsies and suction blisters
can possibly leave a lasting mark on the skin, therefore healthy subjects with
a history of hypertrophic scarring or keloid will be excluded. Furthermore,
patients could experience a (temporary) flare-up of disease related symptoms
and lesions due to interruption of their standard treatment. Drug-related skin
AEs are to be expected in 62% of the treated patients, of which local skin
irritation (20%), itch (18%) and erythema (16%) are most frequently observed.
Additionally, these AEs are frequently anticipated and mitigated in the
outpatient clinic. Drug-related skin AEs are managed according to table 2.
Reference is made to the SmPC for an overview of AEs and associated treatment
related risks.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers must meet all of the following inclusion criteria:
1. Signed informed consent prior to any study-mandated procedure;
2. 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;
3. Body mass index (BMI) >= 18.0 and <= 40.0 kg/m2; during COVID-19 pandemic only
>= 18.0 and <= 33.0 kg/m2
4. No clinically significant skin disease as judged by the investigator
5. No history of hypertrophic scarring or keloid.
6. Subject is willing to refrain from extensively washing (including bathing,
swimming, showering and excessive sweating) the skin 4 hours before every study
visit.
7. 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.
8. 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.
9. Subject is willing and able to washout (topical and oral) antibiotic therapy
for 14 days prior to Day 1.
10. Subject is willing to use effective contraception from screening until EOS
if subject is male or women of childbearing potential
11. Subject has the ability to communicate well with the investigator in the
Dutch language and is willing to comply with the study restrictions.
Eligible MF patients must meet all of the following inclusion criteria at
screening:
1. Signed informed consent prior to any study-mandated procedure;
2. 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
3. Body mass index (BMI) >= 18.0 and <= 40.0 kg/m2; during COVID-19 pandemic only
>= 18.0 and <= 33.0 kg/m2.
4. At least one patch and/or plaque lesion present, with at least one dimension
with a diameter of >= 6cm.
5. Confirmed MF-diagnosis (stage 1a/1b) by histology (or
clinico-histopathological correlation) within the last 10 years.
6. Willing and able to washout any topical treatment for MF (at least 2 weeks)
and any systemic treatment for MF (at least 4 weeks) prior to Day 1, resulting
in a washout of 8 weeks for topical treatment and 10 weeks for disease-related
systemic treatment prior to the first dosing day (day 43).
7. No previous use of CL gel (Ledaga) in the past two years.
8. Subject is willing and able to washout (topical and oral) antibiotic therapy
for 14 days prior to Day 1.
9. Subject is willing to refrain from extensively washing (including bathing,
swimming, showering and excessive sweating) the skin 6 hours before every study
visit day and up to 2 hours after application of the treatment gel.
10. Subject is willing to use effective contraception during the study if
subject is male or women of child bearing potential, for up to 90 days after
the last dose of study treatment
11. Male subjects must be willing to withhold from any sperm donation during
the study and up to 90 days after the last dose of study treatment
Exclusion criteria
Eligible healthy volunteers must meet none of the following exclusion criteria
at screening:
1. History of immunological abnormality (e.g., immune suppression) that may
interfere with study objectives, in the opinion of the investigator.
2. The use of systemic antibiotic therapy for >2 months the past 12 months.
3. 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.
4. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV ab),
or human immunodeficiency virus antibody (HIV ab) at screening;
5. Participation in an investigational drug study within 3 months prior to
screening or more than 4 times a year.
6. Loss or donation of blood over 500mL within three months prior to screening.
7. 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.
8. 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;
9. Pregnant, a positive pregnancy test, intending to become pregnant, or
breastfeeding;
10. Any other known factor, condition, or disease that might interfere with
study conduct or interpretation.
Eligible MF-patients must meet none of the abovementioned and following
exclusion criteria at screening:
1. 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.
2. 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):
a. < 2 weeks for topical treatment, e.g. corticosteroids, retinoids, vitamin D
analogs
b. <4 weeks for phototherapy, e.g. UVB, PUVA, PDT
c. <4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate
d. <6 weeks for peginterferon alfa-2a
e. <8 weeks for radiotherapy or surgery in the treatment area
f. <3 months for any systemic chemotherapeutical treatment
3. Known hypersensitivity to chlormethine gel or its excipients
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-001576-41-NL |
| CCMO | NL77292.056.21 |
| Other | NL9764 and NCT05303480 |
| OMON | NL-OMON22372 |