O6-benzylguanine and Carmustine in Treating Patients With Stage IA-IIA Cutaneous T-cell Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00003613

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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. 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

Condition or Disease	Intervention/Treatment	Phase
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Cutaneous T-cell Non-Hodgkin Lymphoma	Drug: O6-benzylguanine Drug: carmustine Other: laboratory biomarker analysis	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the kinetics of AGT depletion in CTCL skin lesions. II. To determine the toxicity of low dose BCNU plus O6BG.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Trial of O6 Benzylguanine and BCNU in Cutaneous T-cell Lymphoma

Study Start Date :

Apr 1, 1999

Actual Primary Completion Date :

May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (O6-benzylguanine, 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.	Drug: O6-benzylguanine Given IV Other Names: BG Drug: carmustine Given topically Other Names: BCNU BiCNU bis-chloronitrosourea Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (O6-benzylguanine, 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.

Drug: O6-benzylguanine

Given IV

Other Names:

Drug: carmustine

Given topically

Other Names:

BCNU

BiCNU

bis-chloronitrosourea

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Percent decrease of AGT in CTCL skin lesions, obtained from tissue samples [Baseline to 6 weeks]
Point and interval estimates of response using the binomial distribution will be obtained using data from patients with measurable or evaluable disease. If responses occur, then the mean and median duration of response will be determined. Statistical significance will be determined using the t test for analysis of continuous data.
MTD of carmustine estimated as the dose level which is one level below where >= 2 DLT are observed [6 weeks]
Toxicities will be recorded and tabulated. Additional point and interval estimates for the MTD will be obtained using the methods of logistic regression of the proportion of patients experiencing a dose-limiting toxicity of grade >= 2 and by conventional regression of the mean dose-limiting toxicities on dose level.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed CTCL, stages IA-IIA
Performance status ECOG grade 0, 1, or 2
Patients must have recovered from toxicity of prior treatment and have received no CTCL therapy other than emoliation for at least 4 weeks
Patients must have signed a consent form indicating the investigational nature of the treatment and its potential side effects
WBC > 4,000/ul
ANC > 2,000/ul
Platelets > 100,000/ul
Bilirubin < 1.5 mg/dL
SGOT within normal range
Prothrombin time within normal range
Creatinine =< 1.5 mg/dL or creatinine clearance >= 70 ml/min
Calcium and electrolytes normal
Glucose-controlled (diet and insulin) diabetes is permitted
DLCO > 80% normal with the exception of patients who demonstrate clinically normal lung function based on history, physical examination, and chest x-ray as interpreted by the principal investigator
Only those patients with biopsiable tumor and willing to undergo several biopsies will be eligible
Must have failed 1 conventional treatment other than topical corticosteroids; this includes UVB, PUVA, topical mechlorethamine, electron beam, photopheresis, chemotherapy and immuno-modulatory agents such as cytokines

Exclusion Criteria:

Patients with a prior treatment with a nitrosourea
Patients with known central nervous system involvement or primary CNS malignancies will be ineligible
Patients with performance status ECOG grade 3 or 4
Pregnant women, women who are breast feeding infants, or women with reproductive potential not practicing adequate contraception, because of potential toxicity to the fetus or infant
Patients with active infection
Patients with pulmonary disease as determined by history, physical examination, chest X-ray or pulse oximetry
CTCL patients with stage IIB-IVB disease