This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major objectives of this trial are to: 1) determine the kinetics of O6alkylguanine DNA alkyltransferase (AGT) depletion in skin lesions of patients with cutaneous T-cell lymphoma following intravenous administration of 120 mg/m2 of O6benzylguanine; and 2) determine the toxicity of low dose BCNU when administered topically on a biweekly schedule following 120 mg/m2 O6benzylguanine. During the first course of therapy, lesional skin biopsies will be obtained at baseline, and after O6benzylguanine infusion at 6 hrs, 24 hrs and 1 week. These samples will be analyzed for AGT depletion using an enzyme assay, Western blot analysis and quantitative immunohistology. BCNU will be administered topically 1 hr after O6benzylguanine. This will be repeated every 2 weeks until the patient is removed from the trial. BCNU will start at 10 mg, and increase by 10 mg increments at each assigned dose level. BCNU will not be escalated in individual patients. The dose level will be escalated in successive cohorts of three patients as long as no dose-limiting toxicity is observed. If one instance of dose-limiting toxicity is observed among the initial three patients treated at a dose level, then up to an additional 3 patients must be treated at that dose level with no further dose-limiting toxicity in order that dose escalation may proceed. If two instances of dose-limiting toxicity are observed at a dose level, the maximum tolerated dose has been surpassed, and a total of 6 patients must be treated at a previous dose level to assure its tolerability. The GCRC is used for drug administration and pharmacokinetics.
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