Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

O(6)-benzylguanine and Carmustine in Treating Patients With Stage I or Stage II Cutaneous T-cell Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	Over 18	NCI	CASE-CWRU-6496 NCI-T97-0029, NCT00003613, T97-0029, CASE-6496

Objectives

1. Determine the kinetics of O6-alkylguanine DNA alkyltransferase depletion in skin lesions of patients with cutaneous T-cell lymphoma after treatment with O6-benzylguanine.
2. Determine the toxicity of low-dose topical carmustine when administered after O6-benzylguanine in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed cutaneous T-cell lymphoma



• Stage IA, IB, or IIA disease



• Must be able to biopsy tumor



• Must have failed 1 conventional treatment other than topical corticosteroids, including ultraviolet B light, psoralen ultraviolet light, topical mechlorethamine, electron beam, photophoresis, chemotherapy, or immunotherapy agents



• No known CNS involvement or primary CNS malignancy

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• No concurrent hematopoietic growth factors

Chemotherapy:

• See Disease Characteristics
• No prior nitrosoureas

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• At least 4 weeks since any prior therapy and recovered

Patient Characteristics:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm³
• Absolute neutrophil count greater than 2,000/mm³
• Platelet count greater than 100,000/mm³

Hepatic:

• Bilirubin less than 1.5 mg/dL
• SGOT normal
• Prothrombin time normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 70 mL/min

Metabolic:

• Calcium and electrolytes normal
• Glucose-controlled (diet and insulin) diabetes allowed

Pulmonary:

• DLCO greater than 80% (except patients who demonstrate clinically normal lung function based on history, physical examination, and chest x-ray as determined by the principal investigator)
• No pulmonary disease

Other:

• No active infection
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for two months after study therapy

Expected Enrollment

Approximately 20 patients will be accrued for this study within 2 years.

Outcomes

Alkylguanine-DNA alkyltransferase (AGT) modulation as measured by skin biopsy at baseline, 6 and 24 hours, and 1 week after the start of study treatment

Outline

This is a dose-escalation study of carmustine.

Patients receive O6-benzylguanine IV over 1 hour followed by topical carmustine once every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carmustine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for 6 weeks.

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Kevin Cooper, MD, Protocol chair		Ph: 216-844-3111 Email: Kevin.Cooper@uhhospitals.org
Stanton Gerson, MD, Protocol co-chair		Ph: 216-844-8562

Registry Information
Official Title		Phase I Trial of O6Benzylguanine and BCNU in Cutaneous T-Cell Lymphoma
Trial Start Date		1999-01-25
Registered in ClinicalTrials.gov		NCT00003613
Date Submitted to PDQ		1998-09-30
Information Last Verified		2006-12-03
NCI Grant/Contract Number		CA43703, CA62502