O(6)-Benzylguanine and Carmustine in Treating Patients With Stage I or Stage II Cutaneous T-cell Lymphoma - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00003613

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of carmustine given together with O(6)-benzylguanine in treating patients with stage I or stage II cutaneous T-cell lymphoma that has not responded to previous treatment.

Condition	Intervention	Phase
Lymphoma	Drug: O6-benzylguanine Drug: carmustine	Phase I

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Trial of O6Benzylguanine and BCNU in Cutaneous T-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fungal Infections Lymphoma

Drug Information available for: O(6)-Benzylguanine Carmustine

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Alkylguanine-DNA alkyltransferase (AGT) modulation as measured by skin biopsy [ Time Frame: at baseline, 6 and 24 hours, and 1 week after the start of study treatment ] [ Designated as safety issue: Yes ]

Enrollment:	21
Study Start Date:	January 1999
Study Completion Date:	July 2007
Primary Completion Date:	May 2006 (Final data collection date for primary outcome measure)

Intervention Details:

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

Patients receive 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.

Detailed Description:

OBJECTIVES:

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

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

Age:

Over 18

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC greater than 4,000/mm^3
Absolute neutrophil count greater than 2,000/mm^3
Platelet count greater than 100,000/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003613

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Kevin Cooper, MD

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Kevin Cooper, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00003613 History of Changes
Other Study ID Numbers:	CWRU6496, U01CA062502, P30CA043703, CASE-CWRU-6496, NCI-T97-0029, CASE-6496
Study First Received:	November 1, 1999
Last Updated:	June 10, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:

stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma

stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:

Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

Carmustine
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012