Clinical trial NCT03380026
Conditions: Cutaneous T-cell Lymphoma Cutaneous T-cell Lymphoma Stage I Mycosis Fungoides Folliculotropic Mycosis Fungoides Granulomatous Slack Skin Syringotropic Mycosis Fungoides Mycosis Fungoides Variant Transformed Mycosis Fungoides
Keywords: CTCL topical mechlorethamine Valchlor contact dermatitis triamcinolone MF Cutaneous T-cell Lymphoma
Sponsor: Rochester Skin Lymphoma Medical Group, PLLC
Start date: 2017-12-13; Completion date: 2020-12-13
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a two-arm, open-label study that aims to compare the incidence and severity of the most common adverse reactions, particularly contact dermatitis, when Valchlor is used alone or in conjunction with triamcinolone ointment 0.1% in early stage MF subjects (Stage IA and IB) for a period of 4 months.

Detailed description:
Mechlorethamine hydrochloride, or most commonly known as nitrogen nitrogen mustard, was approved by the FDA in 2013 for the treatment of IA and IB Mycosis Fungoides. The most common side effect of Valchlor is a skin rash, which is routinely ameliorated with the application of topical corticosteroids, such as topical Triamcinolone. The main purpose of this study is to determine the efficacy of Triamcinolone in reducing side effects cause by Valchlor and further understand the nature of this skin rash.

This is a split-face study, meaning that subjects will receive both therapies, but limit use to designated areas. Treatment lasts 4 months with follow ups at 5 and 12 months.

Arms: arm 1: 0.016% w/w topical mechlorethamine gel applied over a minimum of 8 cm2, nightly, over a period of 4 months. arm 2: 0.016% w/w topical mechlorethamine gel (once, nightly) and Triamcinolone acetonide 0.1% ointment (up to three times daily) applied in over a minimum of 8 cm2, over a period of 4 months.
Interventions: intervention 1: Triamcinolone intervention 2: Valchlor 0.016 % Topical Gel
Intervention descriptions: intervention 1: Apply up to three times daily on select lesions. intervention 2: Apply valchlor nightly on select lesions.

Protocol documents:
Prot_SAP_000.pdf: 
 
VALCHLOR Therapy in Conjunction with Triamcinolone 0.1% Ointment for the Treatment 
of Contact Dermatitis in Subjects with Early Stage Cutaneous T-cell Lymphoma  
(Mechlorethamine Induced Dermatitis Avoidance Study (MIDAS)) 
Protocol# RSLMG-17.10 
 
Brian Poligone, M.D. Ph.D. 
V. July 11th, 2017 
 
 
 
1. PURPOSE OF THE STUDY AND BACKGROUND 
 
1.1. Purpose of the study 
 
To study the efficacy of Triamcinolone in reducing the adverse effects of Valchlor 
therapy, particularly contact dermatitis in subjects with early stage Mycosis Fungoides.  
 
1.2. Background 
 
Mechlorethamine hydrochloride, commonly known as nitrogen mustard, is an 
alkylating agent that induces apoptosis in malignant T-cells and possibly disrupts 
interactions between keratinocyte-Langerhan cell-T-cell interactions (1).  This agent 
was first used in the late 1950’s as a topical therapy for the treatment of Mycosis 
Fungoides (MF) (2,3).  Initially, its use involved dissolving lyophilized mechlorethamine 
in water and painting it onto the skin (4). However, this use was limited due to high 
rates (67%) of cutaneous hypersensitivity which led to its compounding into an 
ointment (5). Although, this resulted in lower and tolerable rates of delayed type 
cutaneous hypersensitivity (10%), its shelf life remained low. Ointment based 
mechlorethamine only lasted about a week before it started decomposing (6). 
Consequently, mechlorethamine started being prepared in a quick-drying, greaseless 
gel (Valchlor) composed of 0.016% w/w mechlorethamine, a free radical inhibitor 
(butylated hydroxytoluene) and diethylene glycol monoethyl ether. This formulation 
increased permeability into and solubility within the top layer of the skin (stratum 
corneum) making it easier to apply. It also shortens the time of response to treatment 
about 16 weeks earlier than when the ointment is used (7). Valchlor was approved in 
2013 for the treatment of IA and IB MF, but almost a quarter of the subjects enrolled in 
the study (22%) discontinued treatment due to adverse reactions (7).  
The most common adverse reactions were associated with the skin or subcutaneous 
tissue disorders. Contact dermatitis was seen in 56% of the subjects treated with 
Valchlor and 23% of these were moderately severe to severe. Other adverse reactions 
included pruritus (20%), bacterial skin infections (11%), skin ulceration or blistering 
(6%), or skin hypopigmentation (5%). Together, these adverse events encompass 
98% of all adverse events. Despite this, mechlorethamine is usually recommended as 


Page 1 of 28 
 
a primary treatment option for CTCL, as complete responses to topical 
mechlorethamine in early stage MF is associated with a lower risk of disease 
progression (6,8,9). Increasing the probability of subjects achieving a response to 
Valchlor treatment and prevent them from switching therapies could be a possibility if 
skin adverse reactions are managed. This could be done with the use of topical 
corticosteroids. 
Triamcinolone 
0.1% 
ointment 
is 
an 
anti-inflammatory, 
anti-pruritic, 
topical 
corticosteroid with vasoconstrictive actions usually used to treat eczema, dermatitis, 
allergies, and rashes. It’s mechanism of action involves inhibiting the production of 
cytokines that cause inflammation, such as IL-1 (10). In this study, we aim to look at 
the efficacy of Triamcinolone in reducing the adverse effects experienced by MF 
subjects treated with Valchlor, specifically contact dermatitis, pruritus, and skin 
ulceration or blistering.  
 
2. STUDY DESIGN 
 
2.1. Overview 
 
This is a two-arm, open-label study that aims to compare the incidence and severity of 
the most common adverse reactions to Valchlor therapy when used with or without 
triamcinolone ointment 0.1% in early stage MF subjects (Stage IA and IB) for a period 
of 4 months.  
 
2.2. Rationale for Study Design 
 
This study consists of two different therapies administered concurrently to the same 
subject but on different, discrete, skin lesions.  A minimum of 8 cm2 will be chosen for 
each treatment arm (Valchlor only or Valchlor and Triamcinolone ointment 0.1%). 
Lesions must have similar characteristics (scaliness, erythema, hyper-(hypo-) 
pigmentation, elevation, and total size) and location, and must be representative of the 
disease. Lesions treated with different treatments should be at least 10 cm away from 
each lesion. Treatment length will consist of 4 months, as most of the adverse effects 
experienced in subjects treated with Valchlor happened within the first 2 weeks of 
treatment and up to 89% of these occurred within the first four months.  
  
Primary Objective:  
 
To determine if Triamcinolone 0.1% ointment significantly reduces the incidence of 
dermatitis on subjects eligible to start Valchlor therapy.   
 
Secondary Objective:  
 
To distinguish the nature of contact dermatitis (allergic or irritant) induced by Valchlor 
therapy through skin biopsies, patch testing, and the comparison of genetic variability 
in all T-cell clones form skin biopsies of subject who develop dermatitis vs baseline.   
 
Exploratory Objectives:  
 
To determine the severity of dermatitis among both treatment arms, if any. 


Page 2 of 28 
 
 
To if there is any difference in pruritus and sleep disturbance caused by itch in lesions 
treated with Valchlor therapy and Triamcinolone compared to lesions that are treated 
with Valchlor only.  
 
To determine rate and severity of ulceration and skin blistering, and rate of skin 
hyperpigmentation in both treatment groups.  
 
To measure efficacy of Valchlor therapy with Triamcinolone compared to Valchlor in 
subjects with early stage MF. 
 
Primary Endpoint:  
 
Incidence (percentage) of dermatitis in lesions treated concurrently with Triamcinolone 
0.1% ointment versus those that are not. Dermatitis will be defined as a finding of 
cutaneous inflammatory reaction occurring as a result of treatment. This will be 
assessed as a value of present or not present, and may be confirmed by biopsy of the 
specimen.  
 
Secondary Endpoint:  
 
The presence of allergic vs irritant dermatitis will be characterized through skin 
biopsies sent for pathological review, patch testing, and measuring the genetic 
variability of the T-cell clones through sequencing of the CD3 region of all T-cell clones 
found in skin biopsies collected at timepoints when contact dermatitis develop vs. 
those collected at baseline.  
 
Exploratory endpoints:  
 
SCORAD score differences between lesions treated with Valchlor and Triamcinolone 
versus lesions treated with Valchlor only for a period of 4 months. 
 
To determine if there is any difference in pruritus and sleep disturbance caused by itch 
among lesions treated with Valchlor or Valchlor and Triamcinolone, measured as a 
composite score of pruritus in each individual lesion for each treatment arm over a 
period of 4 months.  
 
To determine rate (%) and severity of ulceration and skin blistering, and rate of skin 
hyperpigmentation in both treatment groups over a period of 4 months.  
 
Efficacy of Valchlor therapy with Triamcinolone compared to Valchlor over a period of 
4 months using CAILS. 
 
2.3. Rationale for Dosage 
 
Valchlor and Triamcinolone 0.1% ointment will be administered as described in their 
packaged inserts.  
 
 
 
 


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3. CHARACTERISTICS OF THE RESEARCH POPULATION 
 
3.1. Subject Characteristics 
 
a) Number of Subjects:   
 
Based on statistical analysis performed (Section 13.1), we will need 22 evaluable 
subjects in this study to have a statistically significant difference between both 
treatments. We may recruit up to 28 subjects in this study to account for retention rate.  
 
b) Gender and Age of Subjects 
 
Males and females of 18 years of age or older will be eligible to participate in this 
study.  
 
c) Racial and Ethnic Origin:   
 
All races and ethnicities will be recruited.  
 
3.2. Inclusion and Exclusion Criteria 
 
a) Inclusion Criteria:   
 
• 
Be eligible to receive Valchlor therapy.  
• 
Be at least of 18 years of age and ability to give informed consent 
• 
Have stage IA or IB CTCL 
• 
Subjects with histologic variants of Mycosis Fungoides such as 
folliculotropic, granulomatous slack skin, syringotropic MF, or large cell 
transformation are eligible.  
• 
A skin biopsy within the last 60 days before start of treatment. In cases with 
equivocal histological features, the diagnosis may be confirmed with 
clinicopathologic and/or genetic testing consistent with the National 
Comprehensive Cancer Network guidelines for Mycosis Fungoides. If 
sufficient tissue is not available to perform genetic testing, a new biopsy will 
be performed even if the subject has had a biopsy within 60 days of start of 
treatment. 
• 
Females of child bearing potential must agree to use two highly effective 
methods of contraception (strongly recommended that one of the two forms 
of contraception be non-hormonal such as condom plus spermicide, 
condom plus diaphragm with spermicide, or have a vasectomized partner) 
or use an intrauterine device until 30 days after the last day of drug 
administration. Perimenopausal women must be amenorrhoeic for at least 
12 months to be considered of nonchildbearing potential.   
• 
Males with female partners of child bearing potential must agree to sexual 
abstinence or use two reliable forms of effective contraception 
simultaneously (strongly recommended that one of the two forms should be 
non-hormonal as described above) during the entire treatment period and 
30 days after the last dose.  
• 
Must be able to comply with the study instructions, apply the study 
medication as directed, and attend all visits.  


Page 4 of 28 
 
• 
Willingness to avoid sun exposure and UVB light in areas to be treated. 
b) Exclusion Criteria:  
 
• 
Have been treated with topical mechlorethamine within 6 months in lesions 
followed during this study. 
• 
Have received any topical therapy directed against MF within 2 weeks of 
start of treatment in areas intended to be treated in this study.   
• 
Have received any systemic therapy (oral or injectables) within 3 weeks of 
start of treatment.  
• 
Not have any intercurrent illness or infection that would interfere with study 
participation 
• 
Known hypersensitivity to mechlorethamine or triamcinolone.   
• 
Breastfeeding, pregnancy, or intention to become pregnant. 
 
 
3.3. Discussion of Subject Population 
 
Inclusion and Exclusion Criteria are designed for a specific population who can receive 
the drug. While Valchlor is a topical agent and has not been detected systemically in 
prior studies when applied topically, fetal harm and malformations have been reported 
for systemic administration of mechlorethamine (11). Mechlorethamine was 
teratogenic and embryo‐lethal after a single subcutaneous administration to 
animals.   Therefore, adequate forms of contraception are described in the eligibility 
criteria and have excluded pregnancy or those who intend to become pregnant in this 
study.  
 
Subjects must also have not obtained treatment that could blur the results of the study. 
Therefore, washout periods are essential and an adequate plan to exclude those who 
received potential therapies that could blur results need to be in place.  
 
 
4. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT 
 
4.1.  
Method of Subject Identification and Recruitment 
 
Subjects will be recruited through the site’s clinic, through an principal investigator 
and/or investigator letter sent to physicians around the area for referrals, online 
advertisement, and flyers. All material that would directly reach to potential subjects 
must be approved by the ethical review board prior to distribution.  
 
 
4.2.  
Process of Consent 
 
Only individuals who are delegated authority by the PI are authorized to obtain 
consent. The process will be free of coercion and undue influence, and will provide 
enough information and sufficient time to be conducive to rational and thoughtful 
decision making by the subject. Subjects will be given a copy of the IRB approved 
informed consent at least 24 hours for review of the document, and will be encouraged 
to discuss this study with family and friends.  
 
Subjects will then be walked through the consent form in a private room, be reminded 
that participation in this study is entirely voluntary, and his/her decision will not affect 


Page 5 of 28 
 
the care which he/she is entitled in any way. Subjects can withdraw at any time. 
 
The nature of the study, its purpose, the procedures involved, expectation of duration, 
potential risks and benefits, and any potential discomfort should be explained. The 
informed consent should be approved by the IRB and should be written in non-
technical language.  
 
The person obtaining consent will assess subject understanding before the consent 
form is signed and dated by the subject as well as make sure that all the subject’s 
questions have been answered. No study related procedures can be made before 
consent is obtained.  
 
5. METHODS AND STUDY PROCEDURES 
 
The screening visit will be held 30 days or less prior to pre-treatment. From then 
onwards, visits will be held monthly, with unscheduled visits if necessary for up to four 
months.  
 
The following procedures will be done at the following visits:  
 
Screening Visit (30 days or less prior to baseline visit):  
 
• Informed Consent 
• Inclusion/Exclusion Criteria  
• Measurement of vitals (weight, height, heart rate, blood pressure, and 
respiratory rate). 
• Subjects will be put in to a gown for a CTCL physical examination 
• Medical history and demographics (DOB, race, sex, ethnicity) 
• Adverse event (AE) evaluation  
• Review of concomitant medications  
• Review of prior CTCL therapies 
• Urine or Serum pregnancy test (females of child bearing potential only) 
• Identification of potential lesions to be treated 
• Two 3mm or one 6mm skin biopsy(-ies) will be performed if not done within 
60 days of starting treatment for diagnostic and clone testing. Pathology read 
and immunohistochemistry will be performed on the sample. The skin biopsy 
must be taken from lesions that have not been treated topically for at least 
two weeks. Consequently, skin biopsies may happen at Screening or 
baseline visits including anytime between these visits.  
 
If subject meets enrollment criteria:  
 
Baseline visit (+/- 3 days):  
 
• CTCL specific physical examination and vitals 
• Photographs (individual lesions)  
• CAILS assessment 
• mSWAT 
• VAS 
• SCORAD assessment  
• Physician Global Assessment 


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• Dispensing of drug and drug log 
• AE assessment  
• Review of concomitant medications 
• A demo tube may be used to show subjects how to apply the drug at night 
• A body map (as shown in Appendix 2) will be given to the subject with 
labeling on which treatment(s) goes on what lesions for compliance. 
• Provide 
written 
instructions 
about 
administration 
and 
storage 
of 
investigational products 
• Urine or serum pregnancy test (if needed) 
• $50 compensation 
• Skin Biopsy (if necessary) 
 
 
Day 28 visit (+/- 3 days):  
 
• Physical examination specific to study treatment plus vitals 
• Photographs 
• CAILS assessment 
• mSWAT 
• VAS 
• SCORAD assessments 
• Physician Global Assessment 
• Dispensing of drug 
• Drug accountability and compliance 
• AE assessment 
• Review of concomitant medications 
• Skin biopsy (if needed for contact dermatitis) 
• Urine or serum pregnancy test (if needed) 
• $50 compensation 
 
Months 2 and 3 (+/- 3 days):  
 
• Physical examination specific to study treatment plus vitals 
• Photographs 
• CAILS assessment 
• mSWAT 
• VAS 
• SCORAD assessment 
• Physician Global Assessment 
• Dispensing of drug 
• Drug accountability and compliance 
• AE assessment 
• Review of concomitant medications 
• Skin biopsy (if needed for contact dermatitis) 
• Urine pregnancy test (if needed) 
• $50 compensation 
 
 
 
 
 


Page 7 of 28 
 
 
Month 4 (EOT, +/- 3 days):  
 
• Physical examination specific to study treatment plus vitals 
• Photographs  
• CAILS assessment 
• VAS 
• mSWAT 
• SCORAD assessment  
• Physician Global Assessment 
• Drug accountability and compliance 
• AE assessment 
• Review of concomitant medications 
• Two 3mm skin biopsies of Valchlor only treated lesion (for H&E, and 
Immunoseq) 
• Two 3mm skin biopsies of Valchlor and TAC lesion (for H&E and 
Immonoseq) 
• Urine or serum pregnancy test (if needed) 
• $50 compensation 
 
Follow-up visit (Months 5 and 12 +/- 7 days after last dose):  
 
• Physical Examination 
• Vitals 
• Photographs 
• CAILS assessment  
• mSWAT 
• VAS 
• SCORAD assessment  
• Physician Global Assessment 
• AEs assessment  
• Review of concomitant medications   
• $50 compensation 
• Urine or serum pregnancy test (if needed)  
 
Unscheduled visits might have any of the procedures mentioned above if PI 
determines them necessary. If clinical progression is noted at any time prior to the 
scheduled assessments for efficacy, CAILS and skin photographs, and any standard 
of care procedure that the PI seems appropriate, should be done at that time to fully 
document disease progression. If a biopsy is done for contact dermatitis, then some of 
this tissue will be sent for immunosequencing as well.  
 
Patch Testing 
 
If a subject develops dermatitis suspected to be due to mechlorethamine treatment, an 
optional patch testing of the subject may occur at any time during the study period.  
Standard patch testing is where a small concentration of mechlorethamine will be 
placed on the skin for approximately 48 hours.  Clinical follow up occurs both when 
patches are removed from the skin (at approximately Day 2, 48 hours+/- 24 hours) and 
at Day 4, 96 hours (+/- 24 hours).  General patch testing requires a visit on Days 0 
(patches are placed and initial consultation), Day 2(patches removed and first 


Page 8 of 28 
 
evaluation-early response), and Day 4(second evaluation-delayed response). Patch 
testing to mechlorethamine will be provided at varying concentrations. The subject will 
present for patch testing on a Monday (Day 0), Wednesday (Day 2), and Friday (Day 
4) of one week. A skin biopsy sample will be collected for immunosequencing.  
 
5.1. Treatment Dosage and Administration 
 
This study consists of two different therapies administered concurrently to the same 
subject but on different, discrete, skin lesions.  
 
A minimum of 8 cm2 will be chosen for each treatment arm. Lesions treated with 
different treatments should be at least 10 cm away from each other. 
 
Lesions 
must 
have 
similar 
characteristics 
(scaliness, 
erythema, 
hyper(hypo)pigmentation, elevation, and total size) as well as location. Lesions must 
be representative of the disease and not be in face, axillae, or intertriginous groin.  
 
Treatment length will consist of 4 months, as most of the adverse effects experienced 
in subjects treated with Valchlor happened within the first 2 weeks of treatment and up 
to 89% of these occurred within the first four months. 
 
Valchlor will be applied topically to affected areas at night. It must be applied at least 4 
hours before or 30 minutes after showering or washing. Treated areas will need to dry 
for 10 minutes after application before covering with clothing.  
 
Triamcinolone will be applied 30 min after taking a shower on a minimum of 8 cm2 per 
treatment arm. Lesions treated with different treatments should be at least 10 cm away 
from each lesion. 
 
Table 1. Regimen Description 
 
Agent 
Premedications; 
Precautions 
 
Dose 
 
Route 
 
Schedule 
Cycle 
Length  
Valchlor 
Keep 
refrigerated. Use 
immediately after 
removal from 
refrigerator or 
within 30minutes. 
Do not apply to 
face, axillae, or 
groin area  
Wash hands 
thoroughly after 
application.   
0.016% w/w 
mechlorethamine 
gel 
Topical Every day 
at night 
1 
month 
Triamcinolone Apply on 
completely dry 
skin 30 minutes 
after 
washing/taking a 
shower.  
0.1% ointment 
Topical Up to 
three 
times 
daily 
 


Page 9 of 28 
 
 
A body map will be given to the subject with areas labeled with each treatment 
assigned; to ensure he/she applies the correct drug on the correct lesion. Subjects 
will be instructed to report to the study staff if a mistake was made when applying 
either Valchlor or Triamcinolone.   
 
Treatment with Valchlor will be stopped for any grade of skin ulceration, blistering, 
or moderately-severe or severe dermatitis (i.e. marked skin redness with edema).  
 
Treatment limiting AEs will be grade 3 or 4 local dermal irritations that do not 
resolve to a grade 2 or lower within two weeks off the study drug.  
 
Treatment frequency will be suspended or reduced for a maximum period of 4 
weeks and resumed after irritation improves to a grade 2 or lower. Once AE 
improves, treatment can be restarted at a frequency of once every 3 days. After 
one week, and if dose is tolerated, dose will be increased every other day per week 
and then applied daily if drug is tolerated.  
 
The use of corticosteroids for the treatment of skin irritation in lesions receiving only 
Valchlor is not accepted. Topical emollients or topical antihistamines are permitted. 
 
Subjects with positive-patch test results (allergic contact dermatitis) associated with 
grade 3 or 4 reactions will be withdrawn from the study.  
 
Triamcinolone will first be applied to select lesions in the morning, once daily and 
used up to three times daily if it helps tolerate any adverse reactions induced by 
Valchlor. Triamcinolone will not be used any more frequently than stated in the 
package insert. Treatment limiting AEs would be the development of striae, miliaria, 
and allergic contact dermatitis.  These scenarios are rare. In the case of striae and 
miliaria, subjects will be dose reduced to three times a week. If an allergic contact 
dermatitis develops, the subjects will be removed from the study. 
 
5.2. Efficacy Assessments 
 
Evaluation of Skin Disease 
 
Skin Biopsy 
 
If histological diagnosis of CTCL has not been confirmed within 60 days of the Pre-
treatment visit, a biopsy should be done if PI determines necessary. Subjects must 
have appropriate staging to meet study inclusion criteria. If not enough tissue is left 
over for immunosequencing, an additional biopsy will be required. The skin biopsy 
must be taken from lesions that have not been treated topically for at least two weeks. 
Consequently, skin biopsies may happen at Screening or baseline visits including 
anytime between these visits.  
 
Subsequent biopsies to confirm a complete response, transformation of disease, 
disease progression, or skin rash/dermatitis can be performed at the discretion of the 
principal investigator and/or investigator.  
 
 


Page 10 of 28 
 
 
Skin Biopsies for Clone Testing 
 
Skin biopsies will help determine if malignant clones are present before and after 
treatment, and assess how these differ per treatment arm. This will be done in 
collaboration with Adaptive Biotechnologies (12).To profile the contact dermatitis, 
immunosequence of contact dermatitis skin samples will also be done. Left over DNA, 
protein, and tissue will be stored for future research with appropriate consent from 
subjects. 
Skin Photographs 
 
Lesions to be treated during this study will be selected at baseline. These will be 
measured and photographed using a digital camera dedicated for the study.  
 
Skin photographs should be obtained prior to administration of study drug on Day 1 of 
the first treatment cycle and then as specified in the study procedures. 
 
Special care should be taken to shield the subject’s identity. Preference to lesions that 
are not within or close to tattoos should be given, if applicable. Pictures will then be 
modified to cover identifying tattoos or unique traits (if possible) if they result in a 
publication. 
 
Composite Assessment of Index Lesion Severity (CAILS) 
 
CAILS is an objective, quantitative, method to assess the extent of skin lesions. Skin 
lesions and erythema will be evaluated using CAILS (13). Two CAILS will be done, 
one for each treatment arm. An area of at least 8cm2 for each treatment arm will be 
compared. Lesions treated with different treatments should be at least 10cm away 
from each lesion.  
 
Individual index lesion clinical signs and symptoms will be graded at each visit 
according to the scales found in Tables 2 and 3. A Composite Assessment will be 
generated for each time point by a summation of the grades for each index lesion 
erythema, scaling, plaque elevation, hypopigmentation or hyperpigmentation, and area 
of involvement. The index lesion grade at baseline will be divided into the grade at 
each subsequent study visit to determine the subject’s response to treatment. Any 
ratio of the grade obtained at the visit vs. the one obtained at baseline that is >1.0 will 
indicate worsening of disease.  
 
Based upon the ratio and the absence or presence of other disease manifestations, 
the CTCL response to treatment according to the composite assessment endpoint will 
be classified by the best to worst response hierarchy of CR, PR, SD, or PD, with the 
exception that if PD precedes a better response (CR, PR, or SD) the subject will be 
classified as PD, even if the subject meets response criteria subsequent to the 
progressive disease. Confirmation by at least two assessments separated by at least 
four study weeks is required for a partial or complete response classification. If a PR or 
CR is achieved prior to a PD, and subject then meets PD criteria, these will be 
considered a relapse.  
 


Page 11 of 28 
 
The evaluations of index lesions should be made with non-leading (non-directive) 
questions of symptoms to the subject. Examples of symptom-related events should be 
elicited from the subject to substantiate grading severity. Observations of index lesion 
clinical signs and determination of the index lesion areas should be made with the 
subject as fully undressed as necessary to evaluate all index lesion areas.  
 
To determine the area of index lesions, the longest diameter and the longest diameter 
perpendicular to this diameter of each index lesion will be measured to the nearest 
millimeter. The lesion area will be the product of these two diameters and then graded 
as in Table 2. If there is central clearing of an index lesion (clearing of disease within 
the outer boundaries of the lesion), then the product of the largest perpendicular 
diameters of the area(s) of clearing will be subtracted from the area determined from 
the outer boundary diameters before assigning the appropriate grade as in Table 2.  
 
Table 2. Grading Scales for Composite Assessment of Index Lesion Clinical 
Signs 
 
Lesion Type 
Abnormal Skin 
Scaling 
0 No evidence of scaling on the lesion 
1a  
2 Mild: Mainly fine scales; lesion partially covered 
3a 
4 Moderate: Somewhat coarse scales; lesion partially covered; 
rough surface 
5a 
6 Severe: Coarse, thick scales, virtually all of the lesion 
covered, rough surface. 
7a 
8 Very severe: Coarse, very thick scales; all of the lesion 
covered; very rough surface 
Erythema 
0 No evidence of erythema, possible brown hyperpigmentation 
1a  
2 Mild: Light red lesion 
3a 
4 Moderate: Red Lesion 
5a 
6 Severe: Very Red Lesion 
7a 
8 Very severe: Extremely Red Lesion 
Plaque/Tumor 
Elevation 
0 0mm: No evidence of plaque above normal skin level 
1a ≥0 to <0.5mm: minimal but definite plaque elevation above 
normal skin level 
2 ≥0.5 to <1mm: Slight but definite plaque elevation 
3a ≥1 to <1.5mm: Mild Elevation 
4 ≥1.5 to <2mm: Moderate Elevation 
5a ≥2 to <2.5mm: Moderate to Marked Elevation 
6 ≥2.5 to < 3mm: Marked Elevation 
7a ≥3 to < 3.5mm: Very marked elevation 
8 ≥3.5mm: Extreme elevation 
Index Lesion 
 0 0 cm2 (no measurable area)  


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Area 
 1 > 0 and ≤ 4 cm2  
 2 > 4 and ≤ 10 cm2  
 3 >10 and ≤ 16 cm2  
 4 >16 and ≤ 25 cm2  
 5 >25 and ≤ 35 cm2 
 6 >35 and ≤ 45 cm2  
 7 >45 and ≤ 55 cm2  
 8 > 55 and ≤ 70 cm2  
 9 >70 and ≤ 90 cm2  
 10 >90 and ≤ 110 cm2  
 11 >110 and ≤ 130 cm2  
 12 >130 and ≤ 155 cm2  
 13 >155 and ≤ 180 cm2  
 14 >180 and ≤ 210 cm2  
 15 >210 and ≤ 240 cm2  
 16 >240 and ≤ 270 cm2  
 17 >270 and ≤ 300 cm2  
 18 >300 cm2 
a Intermediate intervals 1, 3, 5 and 7 are to serve as mid-points between the 
defined Grades 0, 2, 4, 6 and 8.  
 
 
Table 3. Response Criteria for Skin 
 
Response 
Description 
Complete Response (CR) 
CA ratio = 0, no clinically abnormal lymph 
nodes (and no cutaneous tumors, or 
known pathologically positive lymph nodes 
or visceral disease, or other tumor 
manifestations) are found, and a 
cutaneous biopsy documenting absence 
of histologic signs of CTCL from a cleared 
lesion is obtained  
Partial Response (PR) 
If the CA ratio is ≤ 0.5 and there is a < 
25% increase in the number or aggregate 
area of clinically abnormal lymph nodes, 
cutaneous tumors, or known 
pathologically abnormal lymph nodes or 
visceral disease; and no new 
pathologically abnormal lymph nodes or 
new visceral disease in a location  
where prior evaluation for disease 
documents the absence of disease within 
30 days of entry in the study  
 
Stable Disease (SD)  
 
If none of the other response 
classifications (i.e., CR, PR, or PD) 
accurately describe the disease status, 
then the response classification is SD. 
 


Page 13 of 28 
 
Progressive Disease (PD) 
If the CA ratio is ≥ 1.25, or there is a ≥ 
25% increase in the discrete number of  
or aggregate area of clinically abnormal 
lymph nodes, cutaneous tumors, known 
pathologically abnormal lymph nodes or 
known visceral disease; or a new 
cutaneous tumor or new pathologically 
positive lymph node or new visceral 
disease in an area documented to be free 
of disease within 30 days of entry in the 
study  
 
 
Modified Skin Weighted Assessment Tool (mSWAT):  
 
The mSWAT will be used to quantify overall disease involvement in the whole body. 
This tool uses the total area of skin involved based on the body surface area. Lesions 
are weighted by lesion characteristic (patch, plaque, and tumor).   
 
 
Table 4. mSWAT 
 
Subjects will be monitored for overall disease burden throughout the study for safety. 
The following response criteria as assessed by mSWAT will be followed:  
 
 


Page 14 of 28 
 
Table 5. Response, as assessed by mSWAT  
Response 
Definition 
CCR 
100% clearance of skin 
PR 
50 to 99% clearance of skin disease from baseline without new tumors 
(T3) in subjects with T1, T2, T4 only skin disease 
SD 
<25% increase to <50 clearance in skin disease from baseline without 
new tumors (T3) in subjects with T1, T2, or T4 only skin disease 
PD 
≥25% increase in skin disease from baseline or development of new 
tumors in those with T1, T2, T4 only skin disease, or loss of response: 
in those with a CR or PR, increase of skin score of greater than the 
sum of the nadir plus 50% baseline score. 
Relapse 
Any disease recurrence in those with a CR 
SCORAD (SCORing Atopic Dermatitis) tool  
The extent of dermatitis on subjects will be measured using SCORAD. This tool will be 
used to determine the severity of the dermatitis.  
Given that only specific lesions on the body of each subject will be treated, we will 
consider a maximum score of 100% if the total body surface area treated by specific 
treatment is covered by dermatitis.  This will be determined by calculating the 
percentage of skin that is covered by dermatitis depending on surface area. This will 
be score “A”.  
The intensity criteria are met by scoring Erythema, Edema/papulation, oozing/crusting, 
excoriation (scratch marks), xerosis (dryness), and thickness on a scare of 0-3 
(0=None, 1=Mild, 2=Moderate, 3=Severe). A lesion that is representative of most of 
the subject's dermatitis should be chosen (not the worst or the best-looking lesion). 
Xerosis must be scored on an area of skin without inflammation. 
These are then added up to give a total score of “B”.  
Subjective symptoms of pruritus and insomnia are then scored using visual analog 
scales that run from 0-10 (0=none, 10= worst imaginable).  
 
These are then added up to give a total score of “C”. 
 
To calculate the final score the following equation is used:  
 
 Final score = A/5 + 7B/2 + C 
The lowest possible score would be zero and the highest 103. Scored will be graded 
as outlined on table 6 below.  


Page 15 of 28 
 
 
Table 6. SCORAD Score and Severity of Dermatitis Evaluation 
Severity of Dermatitis 
Score 
Mild  
<25 
Moderate 
25-50 
Severe 
>50 
 
 
Pruritus and Insomnia Evaluation 
 
A visual analog scale for each treatment arm will be done at each timepoint.  Subjects 
will be asked what their overall itchiness is in the lesions receiving specific treatment 
(Valchlor only vs Valchlor and Triamcinolone).  
Figure 1. Grading Scale for Index Lesion Pruritus and Insomnia. 
 
 
 
 
Subjects will be instructed to draw a line anywhere along the lines of the VAS scales to 
indicate severity of itch and sleep disturbance. A VAS score for itch intensity will be 
obtained for each lesion treated and summed up.   
 
 
 
Physician Global Assessment:  
 
The physician global assessment (PGA) represents the principal investigator and/or 
investigator’s overall assessment of the extent of improvement or worsening of the 
subject’s cutaneous disease compared with baseline as shown in table 7. This 
assessment is designed to consider all cutaneous lesions, including index and non-
index lesions.  
 
 
 
 
 


Page 16 of 28 
 
 
 
 
 
Table 7. PGA  
Grade 
Description 
Response 
0 completely clear 
No evidence of disease; 100% improvement 
CCR 
1 almost clear 
Very obvious improvement (≥90% to <100%); 
only traces of disease remain 
PR 
2 marked 
improvement 
Significant improvement (≥50% to <90% 
clear); some of disease remains 
 
3 moderate 
improvement 
Intermediate between marked and mild 
(≥25% to <50%) 
 
4 slight improvement 
≥10% to , 25%; significant evidence of 
disease remains 
Stable 
5 no change 
Disease has not changed significantly from 
baseline (10 to -25%) 
 
6 condition worse 
Disease is worse than baseline by ≥25% 
PD 
 
5.3. Safety Assessments 
 
Physical exams, vitals, and CTCL assessments will assess subject safety throughout 
the study. AEs and concomitant medications will be assessed at each subject visit. 
Subjects will be instructed to call to schedule an unscheduled visit if they have 
pertinent problems that cannot wait within the four scheduled visits. Principal 
investigator and/or investigator will determine if subject needs to come in for an 
unscheduled visit for safety.  
 
5.4. Assessment of Subject Compliance 
 
Compliance to study medication will be measured through follow up with a drug log. 
Subjects will be given a log to record each application. This log will be reviewed at 
each scheduled visit.  
 
5.5. Costs to the Subject 
 
Study subjects will not be charged for procedures that are performed solely for 
research purposes such as CTCL and contact dermatitis specific assessments 
(CAILS, SCORAD, photographs, etc), and immunosequencing. Triamcinolone and 
Valchlor will be supplied to subject at no cost. Subjects will be ultimately responsible 
for diagnostic tests, and assessments that would otherwise be performed had the 
subject not been in a research study. Such procedures are considered standard of 
care.  
 
5.6. Payment for Participation 
 
Subjects will receive a compensation of $50.00 per completed visit.  
 


Page 17 of 28 
 
5.7. Return of Individual Research Results 
 
Subjects will not be notified about results of the study. However, a publication at the 
end of the study is expected that will show the results of the study. No personal 
identifying information will be used in publications.  
 
6. CONCOMITANT AND DISALLOWED MEDICATIONS 
 
The following medications are prohibited:  
 
• Any therapy against MF other than the one administered during this study on 
the lesions being evaluated  
• Sun light or UVB exposure on lesions evaluated 
• Subjects may receive other topical treatments in lesions not being followed 
for this study as long as they do not have any systemic effects.   
• The use of systemic steroids 
• Alternative medications, particularly, St. John’s wort.  
 
7. SUBJECT WITHDRAWALS 
 
Subjects will be advised in the written informed consent forms that they have the right to 
withdraw from the study at any time without prejudice. Subjects might be withdrawn from the 
study at discretion of the principal investigator and/or investigator if he determines it is in the 
subject’s best interest to discontinue treatment. Subjects may also be withdrawn from the 
research activities if there is subject non-compliance, worsening of disease, intercurrent 
illness, or pregnancy.   
 
Subjects will not be replaced and data collected with be used in the analysis unless subject 
revokes consent via written form.  
 
8. STUDY DRUG/DEVICE/BIOLOGIC ADMINISTRATION/ASSIGNMENT 
 
8.1. Study Drug/Device/Biologic 
 
Valchlor (please see package insert attached) and Triamcinolone 0.1% ointment 
(package insert also attached). 
 
8.2. Dosage of Study Drug/Biologic 
 
Valchlor will be applied topically every day for 4 months unless instructed otherwise.  
Triamcinolone will be applied topically every day for 4 months, up to three times daily. 
Please refer to section 5.1 for details on dose interruptions and reductions.  
 
8.3. Accountability of Investigational Supplies 
 
Drugs will be stored as described in their package inserts:  
 
Valchlor will be kept refrigerated at temperatures between 2-8°C.  
 
Triamcinolone will be kept at room temperature (15-30°C).  
 


Page 18 of 28 
 
8.4. Subject Withdrawal of Study Drug 
 
Please refer to section 5.1 for details on dose interruptions and reductions.  
 
 
9. SAFETY AND REPORTABLE EVENTS 
 
9.1. Adverse Event Definition 
 
An AE is defined as any untoward medical occurrence in a patient administered a 
pharmaceutical product and which does not necessarily have a causal relationship 
with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including  an abnormal lab finding), symptom or disease temporally associated with 
the use of a medicinal product, whether or not related to the medicinal product.  
 
Each AE must be assessed by the principal investigator and/or investigators as to 
whether or not there is a reasonable possibility of causal relationship to Valchlor, and 
documented as either related or unrelated. The determination of the likelihood that 
Valchlor caused the AE must be provided by an investigator who is a qualified 
physician.   
 
9.2. Serious Adverse Event 
A serious adverse event is defined as any adverse medical experience that results in 
any of the following outcomes:  
 
• Death;  
• Life threatening  
• Hospitalization 
• Inpatient new or prolongation of existing hospitalization;  
• Disability/incapacity 
• Is a congenital anomaly/birth defect, or   
• Requires medical or surgical intervention to prevent permanent impairment or 
damage.  
 
9.3. Recording Adverse Events 
 
The NCI-CTCAE v4.0 system will be used to grade AEs, both clinical and laboratory. 
AEs will be grouped and tabulated by Medical Dictionary for Regulatory Activities 
(MedDRA) preferred terms by system organ class. All subjects will be assessed 
regularly for potential occurrence of AEs from the time following the first dose of study 
drug until 30 days after the last dose or initiation of alternative therapy whichever comes 
first. 
 
The principal investigator and/or investigator will inquire about AEs at all subject visits by 
asking the subject a question such as: “How have you been feeling since your last visit?” 
All AEs, whether observed by the principal investigator and/or investigator or reported by 
the subject, must be collected and recorded on the appropriate AE page of the CRF and 
as appropriate on the SAE form. The collection of AE information commences following 
the subject’s written Informed Consent to participate in the study.  If a subject 
experiences an AE, the subject will receive appropriate treatment and supportive care as 
necessary, and the principal investigator and/or Investigator will continue to follow up 


Page 19 of 28 
 
until there is a return to the subject’s baseline condition, or until a clinically satisfactory 
resolution is achieved. 
 
Timely and complete reporting of all AEs will aid in identifying any untoward medical 
occurrence, thereby allowing: (1) protection of safety of study subjects; (2) a greater 
understanding of the overall safety profile of the study drug; (3) recognition of dose-
related study drug toxicity; (4) appropriate modification of study protocols; (5) 
improvements in study design or procedures; and (6) adherence to worldwide regulatory 
requirements.  
 
All adverse events, whether observed by the principal investigator and/or Investigator, 
elicited from or volunteered by the subject, should be documented.  Each adverse event 
will include a brief description of the experience if no term is available for it, the date of 
onset, the date of resolution, the duration and type of experience, the severity, the 
relationship to investigational products, contributing factors, and any action taken with 
respect to the study drug/device. 
 
Standard medical terminology should be used to document AEs on the CRF. The 
subject’s exact description of the event will be recorded in the source documentation. In 
the case of signs and symptoms, the underlying illness or diagnosis will be recorded as 
the event when known. 
 
All AEs will be graded using CTCAE Version 4.0 as described in Table 8 below:  
 
Table 8. AE Grading Criteria 
 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not Indicated 
Grade 2  
 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADLa 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self care 
ADLb 
 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
a: Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc. 
b: Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden. 
ADL = Activities of Daily Living 
 
For AEs not contained within CTCAE, Version 4.0, the principal investigator and/or 
Investigator will assess the severity/grade of an AE according to the five grades above. 
 
Adverse Event Relationship to Study Drug: 
 
The relationship of each AE to the study drug will be evaluated using the following 
guidelines: 


Page 20 of 28 
 
 
Related 
 
This category applies to any AE (whether serious or not) that appears to have a 
reasonable possibility to the use of Valchlor (i.e., a relationship cannot be ruled out). 
Guidelines to determine whether an event might be considered related include (but are 
not limited to) the following:  
1. There is a temporal relationship between the occurrence of the event and the 
administration of Valchlor.  
2. The event abated (diminished) or disappeared when treatment with Valchlor 
was down-titrated, interrupted, or discontinued.  
3. Positive results in a drug sensititvity test (skin test, etc).  
4. Toxic level of the drug as evidenced by measurement of drug concentrations in 
blood or other bodily fluid.  
 
 
Not Related 
 
An AE (whether serious or not) that does not follow a reasonable temporal sequence 
from administration of the drug or that can reasonably be explained by other factors, 
such as underlying diseases, complications, concomitant drugs and concurrent 
treatments. 
 
9.4. Responsibilities for Reporting Serious Adverse Events 
 
Principal investigator and/or investigator will conduct continuous review of data and 
subject safety. The review will include for each treatment arm: the number of subjects 
enrolled, withdrawals, significant toxicities as described in the protocol, serious adverse 
events both expected and unexpected, dose adjustments, and responses observed. The 
PI maintains a database of all adverse events with toxicity grade and information 
regarding treatment required complications, or sequelae.  
 
• 
Principal investigator and/or investigators are to report the following information 
items to the IRB within 5 days:  
▪ 
New or increased risk. For example, publications indicating a new 
risk, new risk in an investigator brochure, FDA black box warning, new 
risk identified in a data safety monitoring report, information or change 
that adversely affects subject safety, or information or change that 
adversely affects the conduct of the research.  
▪ 
Protocol deviation that harmed a subject or placed subject at risk of 
harm 
▪ 
Protocol deviation made without prior IRB approval to eliminate an 
immediate hazard to a subject 
▪ 
Audit, inspection, or inquiry by a federal agency 
▪ 
Written reports of federal agencies (e.g., FDA Form 483) 
▪ 
Allegation of Noncompliance or Finding of Noncompliance 
▪ 
Unauthorized disclosure of confidential information 
▪ 
Unresolved subject complaint 
▪ 
Suspension or premature termination by the sponsor, principal 
investigator and/or investigator, or institution 


Page 21 of 28 
 
▪ 
Incarceration of a subject in a research study not approved to involve 
prisoners 
▪ 
Adverse events or IND safety reports that require a change to the 
protocol or consent 
▪ 
State medical board actions 
▪ 
Information where the sponsor requires prompt reporting to the IRB 
 
• 
Fatal serious adverse events will be reported within 24 hours of knowledge to  
Actelion. Actelion will expedite reports to the FDA and other regulatory authorities as 
appropriate per local and international regulatory reporting requirements. 
• 
 
 
• 
SAEs that are related and unexpected to the investigational products used in this 
protocol will be reported to the sponsor, IRB, and/or other applicable authorities.  
 
• 
All SAEs that are possibly related to the study medication by the Sponsor-Principal 
investigator and/or investigator, must be reported immediately to Actelion Global 
Drug Safety (GDS) as set forth in the IIS agreement and within 24 hours of 
knowledge of the event. Actelion reserves the right to request additional information 
and clarifications on cases forwarded by the Sponsor-Principal investigator and/or 
investigator. SAE forms should be sent the the following e-mail or fax number:  
 
North America (US and Canada) 
San Francisco, USA  
DrugSafetyUS@actelion.com 
Fax: 1-866-227-5886 
 
The principal investigator and/or investigator is obligated to immediately report any 
SAE occurring at any time after the subject signs the Informed Consent Form and all 
unresolved adverse events should be followed by the sponsor-principal investigator 
and/or investigator until the events are resolved, the subject is lost to follow-up, or 
the adverse event is otherwise explained. At the last scheduled visit, the sponsor-
principal investigator and/or investigator should instruct each subject to report, to the 
sponsor-principal investigator and/or investigator, any subsequent event(s) that the 
subject, or the subject’s personal physician, believes might reasonably be related to 
participation in this study. 
 
 
9.5. Pregnancy Reporting 
 
Any pregnancy occurring during the course of the study, up until 30 days after 
discontinuation of therapy will be reported within 24 hours of the Investigator’s 
knowledge to the Sponsor and regulatory authorities if applicable. Pregnancies will 
be reported using the Actelion Pregnancy Form (Appendix 4) to the following email 
or fax:  
 
DrugSafetyUS@actelion.com 
Fax: 1-866-227-5886 
 


Page 22 of 28 
 
Any pregnancy will be followed until its conclusion and its outcome will be reported to 
the sponsor and regulatory authorities if applicable. 
 
10. RISK/BENEFIT ASSESSMENT 
 
10.1. Potential Risks 
 
Valchlor risks:  
 
• Flammable Gel 
• Embryo-fetal Toxicity 
• Dermatitis  
• Non-melanoma skin cancer 
• Mucosal or eye injury 
• Secondary exposure to Valchlor 
 
Reported in more than or equal to 5% of subjects:  
  
• Dermatitis 
• Pruritus  
• Bacterial skin infection  
• Hematological 
abnormalities 
(decreased 
hemoglobin, 
neutrophils, 
or 
platelets).  
 
Triamcinolone 0.1% ointment Risks:  
 
Triamcinolone Acetonide 0.1% Ointment Risks:  
 
Infrequent reactions to topical corticosteroids that occur more frequently if an occlusive 
dressing is used (listed in decreasing order of frequency): 
 
• Burning 
• Itching 
• Irritation 
• Dryness 
• Folliculitis 
• Hypertrichosis 
• Acneiform eruption 
• Hypopigmentation 
• Perioral dermatitis 
• Allergic contact dermatitis 
• Skin maceration 
• Secondary skin infection 
• Skin atrophy  
• Striae 
• Miliaria 
 
 
Other risks if systemic absorption: 
  
• HPA axis suppression  
• metabolic effects (hypoglycemia, hypokalemia)  


Page 23 of 28 
 
 
 
10.2. Protection Against Risks 
 
Subjects will be followed up after each procedure to ensure safety. Principal 
investigator and/or investigators will pay attention to changes from baseline and use 
standard techniques for skin biopsies and other procedures done.  The subject will 
assume responsibility for payment for the treatment of all adverse events.  
 
 
10.3. Potential Benefits to Subjects 
 
Response to treatment with clearance of disease is possible but uncertain. 
 
10.4. Alternatives to Participation 
 
Available skin-directed therapies such as topical glucocorticoids, carmustine 
(BCNU), psoralen plus ultraviolet-A radiation (PUVA) and electron beam radiation 
therapy (EBT) can improve skin manifestations and induce temporary remissions.   
 
Systemic therapies, such as bexarotene, denileukin diftitox injection, photopheresis, 
systemic mechorethamine, cyclophosphamide, vorinostat and methotrexate are 
typically targeted towards advanced stages of CTCL due to their greater potential for 
toxicity.  Various treatments have also been used in combination. 
 
11. CONFIDENTIALIATY OF DATA AND INFORMATION STORAGE  
 
Confidentiality is the ethical and/or legal right that information, such as research 
data, will be held secret and safeguarded from disclosure unless consent is provided 
permitting disclosure. Informed consent will include HIPAA authorization verbiage. 
 
Upon enrollment, each subject will be assigned a unique subject number (UPN) that 
includes the study number at the front and a three-letter code.  These will be used 
instead of their names whenever possible, such as when filling in study records. The 
master log that will link these codes with the names of each subject will be stored in 
a locked cabinet within a locked office. Case report forms and dedicated study 
camera will be kept in a locked cabinet within a locked office under control of PI and 
study staff delegated authority to take photographs. Case report forms will be kept 
within a locked cabinet in a locked office. Photographs obtained will be stored 
without any personal identifiers in them, except for a three-letter code and number 
assigned to each subject at the start of the study. Only the PI can grant permission to 
research staff to access this data.  
 
12. RESEARCH INFORMATION IN MEDICAL RECORDS 
 
Pathology reports will be stored in the medical record. A note stating that the subject 
is a participant of the study will also be placed on the record. 
 
13. DATA ANALYSIS AND MONITORING 
 
13.1. Planned Statistical Analysis 


Page 24 of 28 
 
Using Fisher’s exact test, we determined that we will need 22 evaluable subjects to get 
an 83% chance of detecting a significant difference at a two-sided 0.05 significance 
level. This assumes that 90% of subjects treated with Valchlor along with triamcinolone 
and 44% of those treated with Valchlor only will not get contact dermatitis. This 
calculation takes into account that 89% of subjects experience AEs in a period of 4 
months when they are on VALCHLOR therapy. 
To look at estimation of response rates for each treatment group: previous data 
suggests that the overall response for Valchlor is 50%. From our experience, the 
response rate for Valchlor plus triamcinolone is about 70%. With 22 subjects per group 
the 95% confidence intervals for the response rates would be expected to have widths 
of 44% for Valchlor (expected CI: 28% - 72%) and 41% for Valchlor plus triamcinolone 
(expected CI: 45% - 86%). These calculations are based on exact binomial Clopper-
Pearson confidence intervals.  
To account for retention rate, up to 28 subjects may be enrolled in this study.  
13.2. Data and Safety Monitoring 
 
Study principal investigator and/or investigators will conduct continuous review of 
subject accrual, eligibility, data collection, and subject safety. Study progress and 
safety will be reviewed in a quarterly basis. All AEs and SAEs that have occurred in 
the prior three months will be reviewed by writing all AEs and SAEs in a cumulative 
spreadsheet listing of all events submitted. A progress report will be written as well. 
AEs and SAEs will be reviewed in order to confirm toxicity grade, expectedness, 
relatedness, sequelae, follow up required, and risk to subjects.  
 
 
 
14. REFERENCES 
 
1. 
Edelson RL. Cutaneous T cell lymphoma: the helping hand of dendritic cells. Ann 
N Y Acad Sci 2001;941:1-11. 
2. 
Haserick JR, Richardson JH, Grant DJ. Remission of lesions in mycosis 
fungoides following topical application of nitrogen mustard. Cleve Clin Q 
1959;26:144-47. 
3. 
Bunn PA, Hoffman SJ, Norris D, Golitz LE, Aeling JL. Systemic therapy of 
cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). 
Annals of internal medicine 1994;121(8):592-602. 
4. 
Sipos K. PAINTING TREATMENT OF NITROGEN MUSTARD IN MYCOSIS 
FUNGOIDES. Dermatologica 1965;130:3-11. 
5. 
Ramsay DL, Meller JA, Zackheim HS. Topical treatment of early cutaneous T-cell 
lymphoma. Hematology/oncology clinics of North America 1995;9(5):1031-56. 
6. 
Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the 
management of mycosis fungoides: update of the Stanford experience. Arch 
Dermatol 2003;139(2):165-73. 
7. 
Lessin SR, Duvic M, Guitart J, et al. Topical chemotherapy in cutaneous t-cell 
lymphoma: Positive results of a randomized, controlled, multicenter trial testing 
the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis 
fungoides. JAMA dermatology 2013;149(1):25-32. 


Page 25 of 28 
 
8. 
Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT. Clinical stage IA 
(limited patch and plaque) mycosis fungoides. A long-term outcome analysis. 
Arch Dermatol 1996;132(11):1309-13. 
9. 
Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome 
of 525 patients with mycosis fungoides and sézary syndrome: Clinical prognostic 
factors 
and 
risk 
for 
disease 
progression. 
Archives 
of 
Dermatology 
2003;139(7):857-66. 
10. 
Claman HN. How corticosteroids work. J Allergy Clin Immunol 1975;55(3):145-
51. 
11. 
FDA. 
2013 
June 
26. 
VALCHLOR 
Package 
Insert. 
 
FDA 
<http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf>. 
Accessed 2015 June 26. 
12. 
Kirsch IR, Watanabe R, O’Malley JT, Williamson DW, Scott L-L, Elco CP, et al. 
TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of 
origin in CTCL. Science Translational Medicine 2015;7(308):308ra158. 
13. 
Stevens SR, Ke MS, Parry EJ, Mark J, Cooper KD. Quantifying skin disease 
burden in mycosis fungoides-type cutaneous T-cell lymphomas: the severity-
weighted assessment tool (SWAT). Arch Dermatol 2002;138(1):42-8. 


 
Appendix 1 Schedule of Activities 
 
 
Visit 
0 
(Screenin
g) 
Day 1 
 
 
Day 
1(Patch 
Testing) 
 
Day 2 
(Patch 
Testing) 
 
Day 4 
(Patch 
Testing) 
Day 28 
Months 2 
and 3 
EoT 
Follow up 
(5 and 12 
months) 
Visit Window 
-30 days 
+/- 3days 
 
 
 
+/- 3days 
+/- 3days 
+/- 3days 
+/- 3 days 
Obtain informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria/Enroll 
X 
 
 
 
 
 
 
 
 
Medical history and demographics 
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
X 
X 
X 
X 
Vital signs 
X 
X 
 
 
 
X 
X 
X 
X 
Skin Biopsy (including Pathology 
read and immunohistochemistry) 
Xa 
Xa 
X 
 
 
Xa 
Xa 
Xba 
 
CAILS + SCORAD+ mSWAT 
 
X 
 
 
 
X 
X 
X 
X 
PGA 
 
X 
 
 
 
X 
X 
X 
X 
Identification of lesions 
X 
X 
 
 
 
 
 
 
 
Pregnancy Test 
X 
X 
 
 
 
Xc 
Xc 
Xc 
Xc 
Study drug dispensing 
 
X 
 
 
 
X 
X 
 
 
Study drug Accountability 
 
 
 
 
 
X 
X 
X 
 
Photographs 
 
X 
 
 
 
X 
X 
X 
X 
Adverse event review 
X 
X 
 
 
 
X 
X 
X 
X 
Immunosequencing 
 
X 
X 
 
 
X 
X 
X 
 
Concomitant Medications 
X 
X 
 
 
 
X 
X 
X 
X 
Patch Testing  
Xc 
Xc 
Xc 
Xc 
Xc 
Xc 
Xc 
Xc 
 
Training on how to apply drug 
 
X 
 
 
 
 
 
 
 
Subject Reimbursement 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a) If PI determines necessary or PRN for contact dermatitis 
b) A total of 2 skin biopsies per treatment arm will be done at the EOT visit. One for pathological review and the other one for immunosequencing. 
c) If PI determines it is necessary


 
Appendix II. Body Map