Mycosis Fungoides
Conditions
Keywords
Mycosis Fungoides, Nitrogen Mustard, Cutaneous T-Cell Lymphoma, CTCL - Mycosis Fungoides
Brief summary
This study will evaluate the efficacy, tolerability and safety of the topical application of mechlorethamine (MCH) formulations in patients with stage I or IIA mycosis fungoides (MF).
Detailed description
The successful use of mechlorethamine (MCH) as a topical agent in the treatment of mycosis fungoides, a form of cutaneous T-cell lymphoma, was first reported in the late 1950s, and provided a rationale for skin-directed chemotherapy that minimized systemic toxicity. Since then, multiple investigators have demonstrated the safety and efficacy of topically applied MCH in the treatment of mycosis fungoides. This study will evaluate the efficacy (non-inferiority), tolerability and safety of topical application of MCH proprietary gel versus a compounded ointment formulation in Aquaphor in patients with stage I or IIA MF.
Interventions
DRUGmechlorethamine-MCH (nitrogen mustard)
All affected areas (lesions) are to be treated once daily for twelve months with mechlorethamine-MCH (nitrogen mustard) 0.02% PG or NM 0.02% AP ointment
Sponsors
Yaupon Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with mycosis fungoides confirmed by a skin biopsy * Stage I or IIA patients must have been treated previously with prior topical therapies including PUVA, UVB, topical steroids, but not NM within the past 2 years, or topical carmustine (BCNU) * Patients must be otherwise healthy with acceptable organ function. * Prior to initiating study therapy, patients must not have had topical therapy within four weeks * Lab values within normal range * Willing/able to give consent * Must use effective means of contraception if of childbearing potential
Exclusion criteria
* Newly diagnosed mycosis fungoides with no prior therapy * A prior history of treatment with topical NM within the past 2 years or topical carmustine (BCNU) * Use of topical or systemic therapies for MF within four (4) weeks of entry in the study * Patients with a diagnosis of stage IIB-IV MF * Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent compliance with the requirements of the treatment program * Pregnant or nursing females, or males and females of childbearing potential, not using an effective means of contraception * Patients who have had radiation therapy within one year of study start * Patients who have a history of a higher T score than T2 or a higher N score than N1 * Patients who do not agree to do all labs at one site
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Response Rates Based on CAILS | Assessment made at Day 1 and every subsequent visit during treatment | The ratio of the response rate of the patients treated with the PG formulation to the response rate of the patients treated with the AP formulation. Skin response determined by at least a 50% reduction from baseline in the Composite Assessment of Index Lesion Severity (CAILS) following up to 12 months of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity-weighted Assessment Tool (SWAT) Within up to 12 Months by 2 or More Consecutive Observations Over at Least 4 Weeks | Assessment made at Day 1 and every subsequent visit during treatment | — |
| Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT) | Baseline to end of therapy | Assessment of lesion distribution and severity. A responder analysis was performed on whether subject achieved at least 50% improvement on scale. This had to be confirmed on at least one visit at least 4 weeks apart. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel Study formulation of mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel | 130 |
| AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor Compounded mechlorethamine-MCH (Nitrogen Mustard)in Aquaphor 0.02% | 130 |
| Total | 260 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 22 |
| Overall Study | Concurrent Illness | 4 | 3 |
| Overall Study | Lack of Efficacy | 4 | 4 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Non-compliance | 2 | 3 |
| Overall Study | Subject's Best interest | 2 | 2 |
| Overall Study | Various | 4 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | AP- Mechlorethamine-MCH (NM) 0.02% Compounded in Aquaphor | PG -Mechlorethamine-MCH (Nitrogen Mustard) 0.02% PG Gel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 43 Participants | 37 Participants | 80 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 93 Participants | 179 Participants |
| Age Continuous | 56.7 years STANDARD_DEVIATION 14.34 | 54.7 years STANDARD_DEVIATION 14.2 | 55.7 years STANDARD_DEVIATION 14.28 |
| Region of Enrollment United States | 130 participants | 130 participants | 260 participants |
| Sex: Female, Male Female | 53 Participants | 53 Participants | 106 Participants |
| Sex: Female, Male Male | 77 Participants | 77 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 108 / 128 | 99 / 127 |
| serious Total, serious adverse events | 0 / 128 | 0 / 127 |
Outcome results
Primary
Ratio of Response Rates Based on CAILS
The ratio of the response rate of the patients treated with the PG formulation to the response rate of the patients treated with the AP formulation. Skin response determined by at least a 50% reduction from baseline in the Composite Assessment of Index Lesion Severity (CAILS) following up to 12 months of treatment
Time frame: Assessment made at Day 1 and every subsequent visit during treatment
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG- Mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel | Ratio of Response Rates Based on CAILS | 76 percentage of participants |
| AP- Aquaphor Formulation Mechlorethamine-MCH (NM) 0.02% | Ratio of Response Rates Based on CAILS | 62 percentage of participants |
95% CI: [0.974, 1.552]ANCOVA
Secondary
Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT)
Assessment of lesion distribution and severity. A responder analysis was performed on whether subject achieved at least 50% improvement on scale. This had to be confirmed on at least one visit at least 4 weeks apart.
Time frame: Baseline to end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG- Mechlorethamine-MCH (Nitrogen Mustard) 0.02% Gel | Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT) | 61 Percent of participants |
| AP- Aquaphor Formulation Mechlorethamine-MCH (NM) 0.02% | Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT) | 60 Percent of participants |
Secondary
Severity-weighted Assessment Tool (SWAT) Within up to 12 Months by 2 or More Consecutive Observations Over at Least 4 Weeks
Time frame: Assessment made at Day 1 and every subsequent visit during treatment