Overview

This trial is active, not recruiting.

Conditions recurrent cutaneous t-cell non-hodgkin lymphoma, stage i cutaneous t-cell non-hodgkin lymphoma, stage ii cutaneous t-cell non-hodgkin lymphoma
Treatments carmustine, laboratory biomarker analysis, o6-benzylguanine
Phase phase 1/phase 2
Sponsor National Cancer Institute (NCI)
Start date January 2010
End date April 2012
Trial size 17 participants
Trial identifier NCT00961220, 3405, 7080, CASE 3405-CC304, NCI-2012-02927, P30CA043703, R21CA115057, U01CA062502

Summary

This phase I/II trial studies the side effects and best dose of carmustine when given together with O6-benzylguanine and to see how well they work in treating patients with stage IA-IIA cutaneous T-cell lymphoma. 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. Giving O6-benzylguanine with carmustine may kill more cancer cells.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive O6-benzylguanine IV over 1 hour and apply topical carmustine to the total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after completing O6-benzylguanine infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
carmustine BCNU
Applied topically
laboratory biomarker analysis
Correlative studies
o6-benzylguanine 6-O-BENZYLGUANINE
Given IV

Primary Outcomes

Measure
Overall Response Rate
time frame: Up to 2 weeks after completion of study treatment

Secondary Outcomes

Measure
Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity
time frame: Baseline
Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity
time frame: 24 hours after the first infusion
Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity
time frame: 48 hours after the first infusion
Changes in AGT (O6-alkylguanine DNA Alkyltransferase) Activity
time frame: 1 week after the first infusion
Changes in the Apoptosis
time frame: at 24 hours after the first infusion
Changes in the Apoptosis
time frame: at 48 hours after the first infusion
Changes in the Cell Cycle/Proliferation
time frame: at 24 hours after the first infusion
Changes in the Cell Cycle/Proliferation
time frame: at 48 hours after the first infusion
Changes in DNA Damage- Cytotoxicity
time frame: 24 hours after the first infusion
Changes in DNA Damage- Cytotoxicity
time frame: 48 hours after the first infusion
Changes in AGT Inactivation in Non-responding Patients
time frame: After first course at 2 weeks
Changes in AGT Inactivation in Non-responding Patients
time frame: After seventh course at 14 weeks

Eligibility Criteria

Male or female participants at least 19 years old.

Inclusion Criteria: - Diagnosis of CTCL stages IA-IIA by histopathology and immunohistochemistry in screening biopsies confirmed at Case Western Reserve University within 6 months of enrollment; biopsies may be performed at the site of collaborating institutions and shipped to University Hospitals of Cleveland-Case Western Reserve University (UHC-CWRU) - Performance status Eastern Cooperative Oncology Group (ECOG) grade 0, 1, or 2 - Patients must have recovered from toxicity of prior treatment and have received no CTCL therapy other than emollition for at least 4 weeks, with the exception of topical corticosteroids, which may be used up to 2 weeks before the trial start date - Patients must have signed a consent form indicating the investigational nature of the treatment and its potential side effects - White blood cell (WBC) at least 3.5 x10E9/L - Absolute neutrophil count (ANC) at least 1.6 x10E9/L - Platelets > 100,000/ul - Bilirubin < 1.5 mg/dL - Serum glutamic oxaloacetic transaminase (SGOT) within normal range - Creatinine =< 1.5 mg/dL - Electrolytes normal - Controlled (diet and insulin) diabetes is permitted - Demonstration of clinically normal lung function based on history and physical examination; patients with clinical evidence of pulmonary disease as determined by the investigator should have baseline lung function tests performed with demonstration of diffusing capacity of the lung for carbon monoxide (DLCO) >= 70%; a DLCO single breath, adjusted for hemoglobin, will be utilized; we will not use DLCO/alveolar volume (VA) for inclusion or exclusion in this study - Patients must have cutaneous disease that is amenable to biopsy and must be willing to undergo several sequential biopsies - Must have failed at least one conventional treatment for CTCL other than topical corticosteroids; this includes phototherapy, topical mechlorethamine, topical or oral bexarotene, radiation therapy, photopheresis, chemotherapy, and immunomodulatory agents such as interferon and other retinoids Exclusion Criteria: - Patients who have received prior treatment with topical or systemic BCNU or other nitrosoureas - Patients with known central nervous system involvement or primary central nervous system (CNS) malignancies - 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 - Patients with an active infection which requires hospitalization, or which may affect the patient's safety if the patient was enrolled - Patients with pulmonary disease as determined by history, physical examination, chest X-ray, or pulse oximetry with < 70% predicted DLCO - CTCL patients with stage IIB-IVB disease

Additional Information

Official title A Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma
Principal investigator Kevin Cooper
Description PRIMARY OBJECTIVES: I. To determine the cutaneous T-cell Lymphoma (CTCL) response rate and safety of O6BG (O6-benzylguanine) /BCNU (carmustine) when given biweekly as two consecutive daily doses. SECONDARY OBJECTIVES: I. To determine the laboratory correlates of clinical response and drug efficacy based upon O6-alkylguanine deoxyribonucleic acid (DNA) alkyltransferase (AGT) activity in CTCL lesions will be examined to determine the effects of consecutive day O6BG administration on the extent and duration of AGT depletion. II. To determine the laboratory correlates of clinical response and drug efficacy based upon degree of induction of apoptosis and cell cycle arrest will be examined 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. III. To determine the laboratory correlates of clinical response and drug efficacy based upon O-6-methylguanine-DNA methyltransferase (MGMT) gene mutations and changes in AGT expression will be examined as potential mechanisms for O6BG resistance in non-responding patients. OUTLINE: This is a phase I, dose-escalation study of carmustine followed by a phase II study. Patients receive O6-benzylguanine intravenously (IV) over 1 hour and apply topical carmustine to the total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after completing O6-benzylguanine infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).