Mechlorethamine Induced Contact Dermatitis Avoidance Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Valchlor Therapy in Conjunction With Triamcinolone 0.1% Ointment for the Treatment of Contact Dermatitis in Patients With Early Stage Cutaneous T-cell Lymphoma (Mechlorethamine Induced Dermatitis Avoidance Study)

Conditions
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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

Intervention / Treatment
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* Drug: Triamcinolone
* Drug: Valchlor 0.016 % Topical Gel


Participation Criteria
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Eligibility Criteria
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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. Willingness to avoid sun exposure and ultraviolet B light in areas to be treated. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, split-face study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valchlor 0.016% Topical Gel<br>0.016% w/w topical mechlorethamine gel applied over a minimum of 8 cm2, nightly, over a period of 4 months. | Drug: Valchlor 0.016 % Topical Gel<br>* Apply valchlor nightly on select lesions.<br>* Other names: mechlorethamine gel;|
| Active Comparator: Valchlor plus Triamcinolone<br>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. | Drug: Triamcinolone<br>* Apply up to three times daily on select lesions.<br>* Other names: Triamcinolone 0.1% ointment;Drug: Valchlor 0.016 % Topical Gel<br>* Apply valchlor nightly on select lesions.<br>* Other names: mechlorethamine gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Moderate to Severe Contact Dermatitis by SCORD Scoring | Incidence of moderate to severe contact dermatitis in patients 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 by the SCORD (SCORing Dermatitis) tool and may be confirmed by biopsy of the specimen. Moderate to Severe Contact dermatitis is defined as >25 by SCORD. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature of Contact Dermatitis (Allergic Versus Irritant) | The presence of allergic versus irritant dermatitis was characterized through skin biopsies sent for pathological review and patch testing. Subjects presenting to the clinic with dermatitis underwent patch testing to determine the presence of allergic vs. Irritant contact dermatitis, and at each case a biopsy sample was taken of the affected area to confirm the diagnosis. Patch testing was assessed by the investigator according to the International Contact Dermatitis Research Group scale, using the following for possible outcomes : ?+ indicates a doubtful reaction, 1+ indicates a weak reaction, 2+ represents a strong reaction, 3+ indicates an extreme reaction, and IR indicates an Irritant reaction. A higher score would indicate a worse outcome. 1-3+ reaction at the 96hr reading was considered positive for allergic contact dermatitis. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTCL, topical mechlorethamine, Valchlor, contact dermatitis, triamcinolone, MF, Cutaneous T-cell Lymphoma