Mechlorethamine Induced Contact Dermatitis Avoidance Study (MIDAS)

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)

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.

Study Overview

• Status: Completed
• Conditions: Mycosis Fungoides; Cutaneous T-cell Lymphoma; Transformed Mycosis Fungoides; Cutaneous T-cell Lymphoma Stage I; Folliculotropic Mycosis Fungoides; Granulomatous Slack Skin; Syringotropic Mycosis Fungoides; Mycosis Fungoides Variant
• Intervention / Treatment: Drug: Valchlor 0.016 % Topical Gel; Drug: Triamcinolone

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Fairport, New York, United States, 14450
      • Rochester Skin Lymphoma Medical Group, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valchlor 0.016% Topical Gel; 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; Apply valchlor nightly on select lesions.; Other Names: topical nitrogen mustard; mechlorethamine hydrochloride; mechlorethamine gel
Active Comparator: Valchlor plus Triamcinolone; 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: Valchlor 0.016 % Topical Gel; Apply valchlor nightly on select lesions.; Other Names: topical nitrogen mustard; mechlorethamine hydrochloride; mechlorethamine gel; Drug: Triamcinolone; Apply up to three times daily on select lesions.; Other Names: triamcinolone acetonide; Triamcinolone 0.1% ointment

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Dermatitis	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.	4 months
Efficacy of Valchlor vs Valchlor Plus Triamcinolone	Efficacy of Valchlor therapy with Triamcinolone compared to Valchlor using a 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. A Composite Assessment will be generated for each time point by a summation of the grades for each index lesion's 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.	4 months

Collaborators and Investigators

• Sponsor: Rochester Skin Lymphoma Medical Group, PLLC
• Collaborators: Rochester General Hospital
• Investigators: Principal Investigator: Brian Poligone, MD, PhD, Rochester Skin Lymphoma Medical Group, PLLC

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Valchlor package insert
• Triamcinolone acetonide information

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): August 3, 2020
• Study Completion (Actual): December 13, 2020

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: triamcinolone; contact dermatitis; MF; CTCL; Cutaneous T-cell Lymphoma; topical mechlorethamine; Valchlor
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Skin Diseases, Eczematous; Lymphoma; Dermatitis; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Dermatitis, Contact; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Alkylating; Alkylating Agents; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Mechlorethamine
• Other Study ID Numbers: RSLMG-17.10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Data will be embargoed until the study site has fully examined it. Expected embargo would be one year from study completion.

Study data that is de-identified will be maintained at the study site. As this field is rapidly changing, if a database is available for safe, public upload at the end of study embargo, it will be uploaded to a national database. Otherwise requests for use of the study data will be accepted at the study site and shared with investigators whose proposed use of data has been approved by an independent institutional review board. Contact addresses and phone numbers will be presented on all publications to assist in this study sharing.

• IPD Sharing Time Frame: Expected embargo would be one year from study completion. De-identified data will be maintained at the study site for 2 years after the study ends. Contact addresses and phone numbers will be presented on all publications to assist in this study sharing.
• IPD Sharing Access Criteria: Data will be shared with investigators whose proposed use of data has been approved by an independent institutional review board.
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No