Mechlorethamine Induced Contact Dermatitis Avoidance Study

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.

• Triamcinolone (Drug), also known as triamcinolone acetonide, Triamcinolone 0.1% ointment: Apply up to three times daily on select lesions.
• Valchlor 0.016 % Topical Gel (Drug), also known as topical nitrogen mustard, mechlorethamine hydrochloride, mechlorethamine gel: Apply valchlor nightly on select lesions.

Primary outcomes

• Incidence of Moderate to Severe Contact Dermatitis by SCORD Scoring [4 months]: 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. A total of 26 participants had evaluable SCORD data available at 4 months for both treatment sides and were included in this analysis. While 28 participants enrolled and 27 had at least one post-baseline assessment, 2 participants withdrew prior to completing the 4-month SCORD evaluation, leaving 26 evaluable subjects.

Secondary outcomes

• Nature of Contact Dermatitis (Allergic Versus Irritant) [Subjects were evaluated for dermatitis at each visit over the 4-month duration of the trial. Monthly study visits at Months 1, 2, 3, and 4. 27 participants had at least one post-baseline measurement and were included in the overall study assessment.]: The presence of allergic versus irritant dermatitis was characterized through skin biopsies sent for pathological review and patch testing. Subjects were evaluated at Screening, Month 1, month 2, month 3, and month 4 visits for incidence of dermatitis. 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. For patch testing, a 1-3+ reaction at the 96hr reading post-application was considered positive for allergic contact dermatitis.

Other outcomes

• Severity of Dermatitis [4 months]: Scoring Atopic Dermatitis (SCORAD) differences between lesions treated with Valchlor and Triamcinolone versus lesions treated with Valchlor only. SCORAD measures the extent and severity of dermatitis. The percentage of total body surface area (0-100) covered by a lesion is measured by an investigator, and this number corresponds to score "A." The intensity criteria are met by scoring erythema, edema/papulation, oozing/crusting, excoriation, xerosis, and thickness on a scale of 0-3 (0=none, 1=mild, 2=Moderate, 3=Severe). These values are summed to give a total score, "B." Subjective symptoms of pruritus and insomnia are then scored using visual analogue scales ranging from 0-10 (0=none, 10=worst imaginable), and the result of each is summed to give score "C". The final score is then calculated by the formula A/5 + 7B/2 + C. The lowest possible score is 0, and the highest possible score is 103. A higher score indicates a worse outcome. A lower score would be a better outcome.
• Efficacy of Valchlor vs Valchlor Plus Triamcinolone [Baseline and Month 4]: CAILS (Composite Assessment of Index Lesion Severity) is calculated per target lesion. Each component (erythema, scaling, plaque elevation, hypo/hyperpigmentation, and surface area) is graded on a scale of 0 to 8. Total CAILS scores range from 0 to 24 per lesion, where a score of 0 represents complete clearing (best outcome) and 24 represents maximum severe disease (worst outcome).

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Incidence of Moderate to Severe Contact Dermatitis by SCORD Scoring (Primary), Number, patients: Valchlor 0.016% Topical Gel 16; Valchlor Plus Triamcinolone 11
• Nature of Contact Dermatitis (Allergic Versus Irritant) (Secondary), Count of units, Incidents of dermatitis: All Participants 2
• Severity of Dermatitis (Other pre specified), Mean, score on a scale: Valchlor 0.016% Topical Gel 24.8 +/- 21.8; Valchlor Plus Triamcinolone 12.7 +/- 13.5
• Efficacy of Valchlor vs Valchlor Plus Triamcinolone (Other pre specified), Mean, CAILS score: Valchlor 0.016% Topical Gel 8.6 +/- 4.2; Valchlor Plus Triamcinolone 7.0 +/- 5.1

Adverse events

Time frame: 12 months

Other adverse events by term

• Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. 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 Dermatol. 2013 Jan;149(1):25-32. doi: 10.1001/2013.jamadermatol.541. PMID 23069814
• Results publication: Alexander-Savino CV, Chung CG, Gilmore ES, Carroll SM, Poligone B. Randomized Mechlorethamine/Chlormethine Induced Dermatitis Assessment Study (MIDAS) Establishes Benefit of Topical Triamcinolone 0.1% Ointment Cotreatment in Mycosis Fungoides. Dermatol Ther (Heidelb). 2022 Mar;12(3):643-654. doi: 10.1007/s13555-022-00681-6. Epub 2022 Feb 5. PMID 35122614

• Study Protocol and Statistical Analysis Plan (PDF, 2017-07-11)

• Brian Poligone, MD, PhD, Principal investigator, Rochester Skin Lymphoma Medical Group, PLLC