Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides

Study Overview
=================
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.

Official Title
-----------------
A Phase II Pivotal Trial to Evaluate the Safety and Efficacy of Nitrogen Mustard (NM) 0.02% Ointment Formulations in Patients With Stage I or IIA Mycosis Fungoides (MF)

Conditions
-----------------
Mycosis Fungoides

Intervention / Treatment
-----------------
* Drug: mechlorethamine-MCH (nitrogen mustard)


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 (PG - NM (MCH) 0.02%)<br>PG - mechlorethamine-MCH (nitrogen mustard) 0.02% gel To evaluate the tolerability and safety of topical mechlorethamine-MCH (nitrogen mustard) 0.02% ointment formulations in patients with stage I or IIA MF | Drug: mechlorethamine-MCH (nitrogen mustard)<br>* 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<br>* Other names: nitrogen mustard;|
| Active Comparator: 2 (AP - MCH(NM) 0.02%)<br>AP - mechlorethamine-MCH (nitrogen mustard) 0.02% compounded in Aquaphor To evaluate the tolerability and safety of mechlorethamine-MCH (nitrogen mustard)0.02% ointment formulations in patients with stage I or IIA MF | Drug: mechlorethamine-MCH (nitrogen mustard)<br>* 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<br>* Other names: nitrogen mustard;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Assessment made at Day 1 and every subsequent visit during treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Baseline to end of therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mycosis Fungoides, Nitrogen Mustard, Cutaneous T-Cell Lymphoma, CTCL - Mycosis Fungoides