Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma
I. To determine the CTCL response rate and safety of O6BG/BCNU when given biweekly as two
consecutive daily doses.
I. To determine the laboratory correlates of clinical response and drug efficacy based upon
the following surrogate marker studies:
- AGT activity in CTCL lesions will be examined to determine the effects of consecutive
day O6BG administration on the extent and duration of AGT depletion.
- Degree of induction of apoptosis and cell cycle arrest will be examined in the
malignant T-cell population of lymphomatous tissue and in the constitutive cells of the
skin to determine drug efficacy and toxicity through immunohistochemical techniques.
- MGMT gene mutations and changes in AGT expression will be examined as potential
mechanisms for O6BG resistance in non-responding patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study of carmustine followed by a
phase II study.
Patients receive O6-benzylguanine (O6BG) IV over 1 hour and apply topical carmustine to the
total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after
completing O6BG infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses
in the absence of disease progression or unacceptable toxicity.
Tissue and blood samples may be collected for further analysis.
After completion of study treatment, patients are followed at 2 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response rate
Response rate and its confidence interval will be estimated based on binomial distribution theory. Statistical pair-wise comparisons of response rates between this phase I/II trial and the 30 and 40 mg (MTD) dose level cohorts from the Phase I trial using chi-square or Fisher's exact test will be performed.
Up to 2 weeks after completion of study treatment
Case Western Reserve University
United States: Food and Drug Administration
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