A Phase II Pivotal Trial to Evaluate the Safety and Efficacy of Notrogen Mustard

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DESCRIPTION (provided by applicant): This application is a 4th year renewal of a FDA-OPD grant, that currently provides funding for a Phase 2, pivotal trial testing the safety and efficacy of topical nitrogen mustard (NM) formulations in patients with mycosis fungoides (MF)(NCT00168064). MF is the most common type of cutaneous T-cell lymphoma with an incidence of about 1,700 new cases annually and prevalence estimated at 16-20,000 cases in the USA. NM (mechlorethamine hydrochloride) is an alkylating agent, used in the systemic treatment of lymphomas. NM compounded into petrolatum or Aquaphor(r) has been shown to be a safe and effective topical treatment of MF in a 0.02-0.04% concentration range; particularly when initial lower concentrations are titrated up to clinical responses at higher concentrations. Despite this clinical experience, 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 available in multiple concentrations would be of benefit by offering a GMP product that would be available through all retail pharmacies. A propylene glycol (PG)-containing ointment formulation has been developed as an alternative to the heavy Aquaphor(r) (AP) vehicle which can be difficult to apply to the skin and can compromise patient compliance. A multi-center, randomized, observer-blind trial has been initiated to test the safety and efficacy of a manufactured 0.02% NM PG ointment versus a compounded 0.02% NM AP ointment. FDA-OPD is funding the two lead sites (Fox Chase Cancer Center and Stanford University) and the industry partner and sponsor (Yaupon Therapeutics, Inc., Radnor, Pa.) is funding eleven additional sites. The initial accrual target of 118 has been increased to 200 to accommodate for withdraws prior to the 12 month treatment period. It is now anticipated that accrual will be completed by year three but assessment will continue into and be completed by year four. Established patients with Stage Ia, Ib or IIa MF are eligible. Primary and secondary efficacy endpoints are the Composite Assessment of Index Lesion Severity (CAILS) and Severity Weighted Assessment Tool (SWAT), respectively. Patients apply study ointment to affected skin areas (lesions) or total skin surface (depending on stage) once daily for up to twelve months. The frequency of application can be adjusted for toxicity. Tumor response and toxicity are assessed every 4 weeks from months 1-6 and every 8 weeks from months 7-12. Additional toxicity data (squamous cell carcinoma) will be captured in an extended twelve-month follow-up. Yaupon Therapeutics, Inc. has secured a Special Protocol Assessment (SPA) and fast track status from the FDA Review Division for this study.