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

Study Overview
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Brief Summary
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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

Detailed Description
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PRIMARY OBJECTIVES: I. 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.

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

Conditions
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Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage II Cutaneous T-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: O6-benzylguanine
* Drug: carmustine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (O6-benzylguanine, carmustine)<br>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<br>* Given IV<br>* Other names: BG;Drug: carmustine<br>* Given topically<br>* Other names: bis-chloronitrosourea;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent decrease of AGT in CTCL skin lesions, obtained from tissue samples | 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. | Baseline to 6 weeks | 
| MTD of carmustine estimated as the dose level which is one level below where >= 2 DLT are observed | 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. | 6 weeks |