NCT00961220

O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma

A Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of carmustine when given together with O6-benzylguanine and to see how well they work in treating patients with stage IA-IIA cutaneous T-cell lymphoma. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help carmustine work better by making cancer cells more sensitive to the drug. Giving O6-benzylguanine with carmustine may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the cutaneous T-cell Lymphoma (CTCL) response rate and safety of O6BG (O6-benzylguanine) /BCNU (carmustine) when given biweekly as two consecutive daily doses. SECONDARY OBJECTIVES: I. To determine the laboratory correlates of clinical response and drug efficacy based upon O6-alkylguanine deoxyribonucleic acid (DNA) alkyltransferase (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. II. To determine the laboratory correlates of clinical response and drug efficacy based upon 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. III. To determine the laboratory correlates of clinical response and drug efficacy based upon O-6-methylguanine-DNA methyltransferase (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 phase I, dose-escalation study of carmustine followed by a phase II study. Patients receive O6-benzylguanine intravenously (IV) over 1 hour and apply topical carmustine to the total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after completing O6-benzylguanine infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2 weeks.

Conditions

• Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
• Stage I Mycosis Fungoides and Sezary Syndrome AJCC v7
• Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7

Interventions

Type	Name	Description
DRUG	Carmustine	Applied topically
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	O6-Benzylguanine	Given IV

Timeline

• Start date: 2010-02-01
• Primary completion: 2012-04-08
• Completion: 2014-04-08
• First posted: 2009-08-18
• Last updated: 2018-05-22
• Results posted: 2015-03-23

Locations

4 sites across 1 country: United States