Cutaneous T-cell Lymphoma, Cutaneous T-cell Lymphoma Stage I, Folliculotropic Mycosis Fungoides, Granulomatous Slack Skin, Mycosis Fungoides, Mycosis Fungoides Variant, Syringotropic Mycosis Fungoides, Transformed Mycosis Fungoides
Conditions
Keywords
CTCL, topical mechlorethamine, Valchlor, contact dermatitis, triamcinolone, MF, Cutaneous T-cell Lymphoma
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.
Interventions
DRUGTriamcinolone
Apply up to three times daily on select lesions.
DRUGValchlor 0.016 % Topical Gel
Apply valchlor nightly on select lesions.
Sponsors
Rochester Skin Lymphoma Medical Group, PLLC
Rochester General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
open-label, split-face study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrian Poligone, MD, PhD
Rochester Skin Lymphoma Medical Group, PLLC
Participant flow
Recruitment details
Patients presenting to medical clinic eligible for mechlorethamine topical therapy.
Pre-assignment details
Two week wash out. Prior to treatment, one half of each patient's body (divided sagittally at the midline) is assigned to treatment with Valchlor only, while the other side of the patient's body is assigned to treatment with both Valchlor and Triamcinolone Acetonide. Group assignment is determined randomly by the flip of a coin.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Group consisting of all trial participants that completed screening and randomization.
In this split-person study, lesions from one half of each participant's body are assigned to one of two treatment groups: One half of the body is assigned to treatment of affected lesions with Valchlor only, while the other half of the body is assigned to treatment of affected lesions with both Valchlor and Triamcinolone.
For the Valchlor only group, Valchlor is applied once nightly to the target lesions.
For the Valchlor + Triamcinolone group, 0.016% w/w topical mechlorethamine gel is applied once nightly to target lesions, and Triamcinolone acetonide 0.1% ointment is applied up to three time per day to target lesions over a minimum of 8 cm2
For both groups, the treatment period spanned four months. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Customized 21-30 | 2 Participants |
| Age, Customized 31-40 | 1 Participants |
| Age, Customized 41-50 | 2 Participants |
| Age, Customized 51-60 | 6 Participants |
| Age, Customized 61-70 | 7 Participants |
| Age, Customized 71-80 | 7 Participants |
| Age, Customized 81-90 | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 16 / 28 | 11 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
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.
Time frame: 4 months
Population: Each patient had both treatments (self-controlled)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valchlor 0.016% Topical Gel | Incidence of Moderate to Severe Contact Dermatitis by SCORD Scoring | 16 patients |
| Valchlor Plus Triamcinolone | Incidence of Moderate to Severe Contact Dermatitis by SCORD Scoring | 11 patients |
Secondary
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.
Time frame: 4 months
Population: All analyzed trial participants Were included in assessment of dermatitis. 12 incidents of dermatitis were observed across the study, and at each incident a biopsy of the affected area was sent for histopathological review. 10 of 12 patients presented with allergic contact dermatitis, while 2 out of 10 12 patients presented with irritant contact dermatitis according to pathology results.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Valchlor 0.016% Topical Gel | Nature of Contact Dermatitis (Allergic Versus Irritant) | Incidents of Contact Dermatitis | 2 Incidents of dermatitis |
| Valchlor 0.016% Topical Gel | Nature of Contact Dermatitis (Allergic Versus Irritant) | Incidents of Allergic Dermatitis | 10 Incidents of dermatitis |
Other Pre-specified
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.
Time frame: 4 months
Population: CAILS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valchlor 0.016% Topical Gel | Efficacy of Valchlor vs Valchlor Plus Triamcinolone | Average CAILS score at Baseline | 8.6 CAILS score | Standard Deviation 4.2 |
| Valchlor 0.016% Topical Gel | Efficacy of Valchlor vs Valchlor Plus Triamcinolone | Average CAILS score at Month 4 | 11.4 CAILS score | Standard Deviation 4.9 |
| Valchlor Plus Triamcinolone | Efficacy of Valchlor vs Valchlor Plus Triamcinolone | Average CAILS score at Baseline | 7.0 CAILS score | Standard Deviation 5.1 |
| Valchlor Plus Triamcinolone | Efficacy of Valchlor vs Valchlor Plus Triamcinolone | Average CAILS score at Month 4 | 12.0 CAILS score | Standard Deviation 4.85 |
Other Pre-specified
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.
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valchlor 0.016% Topical Gel | Severity of Dermatitis | 24.8 score on a scale | Standard Deviation 21.8 |
| Valchlor Plus Triamcinolone | Severity of Dermatitis | 12.7 score on a scale | Standard Deviation 13.5 |