? This is an amended application of a Phase 2, pivotal trial testing the safety and efficacy of topical nitrogen mustard in patients with MF. MF is the most common type of cutaneous T-cell lymphoma with an incidence of about 1,000 new cases annually and prevalence estimated at 16 to 20,000 cases in the United States. Mechlorethamine hydrochloride, commonly known as nitrogen mustard (NM), is an alkylating agent, used in the systemic treatment of lymphomas. Its successful use as a topical agent for treating MF was first reported in the late 1950s. Since then, multiple investigators have demonstrated the safety and efficacy of topically applied NM in MF. Yet, to date there are no FDA approved topical formulations. Therefore, this small patient population relies on compounding pharmacists, where available, in non-GMP environments. An FDA approved topical formulation of NM would be of benefit by offering a GMP product that would be available through all retail pharmacies. ? ? This is a multi-center, randomized, double-blind, placebo-controlled study of patients with previously treated Stage I or II MF. Prior treatments may include topical therapies, but not topical NM, or topical carmustine (BCNU). A Severity Weighted Assessment Tool (SWAT), a determination of the percentage involvement of total body surface area, and, if present, assessment of clinically abnormal lymph nodes (>1 cm diameter) will be completed at baseline (Day 1) and throughout the twelve-month study and at follow-up. Tumor response and toxicity be assessed every 4 weeks from months 1 to 6 and every 8 weeks from months 7 to 12. Additional toxicity data will be captured in an extended twelve-month follow-up. One lesion will be biopsied pre-, during, and post-treatment. Quality-of-life questionnaires will be administered. ? ? A total of 88 patients will be enrolled and randomized with intent to treat. Patients will begin treatment with l5mg% NM ointment applied to affected skin areas (lesions) once daily for up to twelve months. Patients who do not obtain a partial response (>50% improvement) within three months, will be escalated to 30mg% NM ointment daily applications. The frequency of application may be adjusted for toxicity. Patients with progressive disease (>25% worsening) or allergic contact sensitivity and grade 3/4 dermal irritation will be withdrawn and included in the final response assessment. ? ? IND referencing rights will be provided to FCCC by Yaupon Therapeutics, Inc. ? ? The public health impact of this proposal will be that it leads to FDA approval and access to an effective and safe topical therapy (NM ointment) for patients with the orphan disease MF. ? ?
|Lessin, Stuart R; Duvic, Madeleine; Guitart, Joan et al. (2013) 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 149:25-32|