TOPICAL NITROGEN MUSTARD TREATMENT OF MYCOSIS FUNGOIDES*

局部氮芥治疗蕈样肉芽肿*

• 批准号: 7371092
• 负责人: STUART R LESSIN
• 金额: $ 35万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-20 至 2008-03-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371092
• 关键词: TOPICAL; NITROGEN; MUSTARD; TREATMENT; MYCOSIS

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： 这是一项II期关键试验的修订申请，该试验旨在检测MF患者局部使用氮芥的安全性和有效性。 MF是最常见的皮肤T细胞淋巴瘤类型，在美国每年约有1，000例新发病例，估计患病率为16至20，000例。 盐酸氮芥，通常称为氮芥（NM），是一种烷化剂，用于全身治疗淋巴瘤。 其作为治疗MF的局部药剂的成功使用在20世纪50年代末首次报道。 从那时起，多名研究者已经证明了局部应用NM治疗MF的安全性和有效性。 然而，迄今为止还没有FDA批准的局部制剂。 因此，这一小部分患者人群在非GMP环境中依赖于配制药剂师（如有）。 FDA批准的NM局部制剂将通过提供可通过所有零售药店获得的GMP产品而受益。 这是一项在既往接受过治疗的I期或II期MF患者中开展的多中心、随机、双盲、安慰剂对照研究。 既往治疗可能包括局部治疗，但不包括局部NM或局部卡莫司汀（BCNU）。 将在基线（第1天）和整个12个月研究期间以及随访时完成严重性加权评估工具（SWAT），确定全身表面积受累百分比，以及临床异常淋巴结（直径>1 cm）的评估（如果存在）。 从第1个月至第6个月每4周一次评估肿瘤缓解和毒性，从第7个月至第12个月每8周一次评估肿瘤缓解和毒性。 将在延长的12个月随访中采集其他毒性数据。 将在治疗前、治疗期间和治疗后对一处病变进行活检。 将进行生活质量问卷调查。 患者将开始用15mg%NM软膏每天一次涂敷于受影响的皮肤区域（损伤），持续长达12个月。在三个月内未获得部分反应（>50%改善）的患者将逐步增加至每日施用30mg%NM软膏。 可以根据毒性调整施用频率。 具有进行性疾病（>25%恶化）或过敏性接触敏感性和3/4级皮肤刺激的患者将退出并包括在最终反应评估中。 IND引用权将由Yaupon Therapeutics，Inc.提供给FCCC。 该提案对公共卫生的影响将是，它将导致FDA批准并获得孤儿病MF患者的有效和安全的局部治疗（NM软膏）。