O6-Benzylguanine and Topical Carmustine in Early-Stage(IA-IIA) Cutaneous T-Cell Lymphoma - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00961220

Purpose

RATIONALE: 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.

PURPOSE: This phase I/II trial is studying the side effects of giving O6-benzylguanine together with topical carmustine and to see how well it works in treating patients with stage IA or stage IIA cutaneous T-cell lymphoma that has not responded to treatment.

Condition	Intervention	Phase
Lymphoma	Drug: O6-benzylguanine Drug: carmustine Other: laboratory biomarker analysis Procedure: biopsy	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Carmustine

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Overall response rate [ Time Frame: Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical response [ Time Frame: Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression. ] [ Designated as safety issue: No ]
O6-alkylguanine DNA alkyltransferase (AGT) data [ Time Frame: biopsies at baseline, 24 or 48 hours, and 1 week. ] [ Designated as safety issue: No ]
Apoptosis, cell cycle/proliferation, DNA damage data [ Time Frame: biopsies at baseline, 24 or 48 hours, and 1 week. ] [ Designated as safety issue: No ]
AGT inactivation in non-responding patients [ Time Frame: at baseline and 24 hours after the 7th cycle of therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	February 2010
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Intervention Details:

O6-benzylguanine (O6BG) IV over 1 hour. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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.

Detailed Description:

OBJECTIVES:

To determine the response rate and safety of O6-benzylguanine (O6BG) and topical carmustine when given biweekly as 2 consecutive daily doses in patients with refractory stage IA-IIA cutaneous T-cell lymphoma (CTCL).
To determine the laboratory correlates of clinical response and drug efficacy based upon O6-alkylguanine DNA alkyltransferase (AGT) activity in CTCL lesions and the effects of consecutive-day O6BG administration on the extent and duration of AGT depletion.
To determine the laboratory correlates of clinical response and drug efficacy based upon degree of induction of apoptosis and cell cycle arrest 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.
To determine the laboratory correlates of clinical response and drug efficacy based upon MGMT gene mutations and changes in AGT expression 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.

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 (CTCL)
- Early stage (stage IA-IIA) disease
- Refractory disease
Disease amenable to biopsy
Must have failed ≥ 1 conventional treatment for CTCL other than topical corticosteroids, including phototherapy, topical mechlorethamine, topical or oral bexarotene, radiotherapy, photopheresis, chemotherapy, or immunomodulatory agents (e.g., interferon and other retinoids)
No known CNS involvement or primary CNS malignancies

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
WBC > 4,000/µL
ANC > 2,000/µL
Platelet count > 100,000/μL
Bilirubin < 1.5 mg/dL
SGOT normal
Creatinine < 1.5 mg/dL
Electrolytes normal
Diabetes allowed with controlled glucose (diet and insulin)
Clinically normal lung function based on history and physical examination
- Patients with clinical evidence of pulmonary disease, as determined by the investigator, must demonstrate DLCO > 80%
Willing to undergo several sequential biopsies
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infection

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from all prior therapy
No prior CTCL therapy other than emolliation for ≥ 4 weeks
No prior topical or systemic carmustine or other nitrosoureas
At least 2 weeks since prior topical corticosteroids

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00961220

Locations

United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Kevin Cooper, MD 216-844-3111 kevin.cooper@uhhospitals.org

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Kevin Cooper, MD

Case Medical Center, University Hospitals Seidman Cancer 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:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00961220 History of Changes
Other Study ID Numbers:	CASE3405, P30CA043703, R21CA115057, CASE-CWRU-3405, 7080
Study First Received:	August 16, 2009
Last Updated:	February 1, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:

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

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 May 20, 2012