O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-01

Study Completion Date

2014-04-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

O6-benzylguanine and Carmustine in Treating Patients With Unresectable Locally Recurrent or Metastatic Melanoma

NCT00005961

Melanoma (Skin)

COMPLETED PHASE2

Tulmimetostat (DZR123) in Patients With Mycosis Fungoides and Sézary Syndrome

NCT05944562

Mycosis Fungoides Sezary Syndrome Mycosis Fungoides/Sezary Syndrome

RECRUITING PHASE1

Combination Chemotherapy Plus Biological Therapy in Treating Patients With Metastatic Melanoma

NCT00004141

Melanoma (Skin)

COMPLETED PHASE2

Dacarbazine and Carmustine in Metastatic Melanoma

NCT01692691

Melanoma Metastatic

TERMINATED PHASE2

Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma

NCT01838200

Metastatic Melanoma

TERMINATED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Stage I Mycosis Fungoides and Sezary Syndrome AJCC v7 Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (O6-benzylguanine, carmustine)

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.

Group Type EXPERIMENTAL

Carmustine

Intervention Type DRUG

Applied topically

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

O6-Benzylguanine

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Carmustine

Applied topically

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

O6-Benzylguanine

Given IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

BCNU Becenum Becenun BiCNU Bis(chloroethyl) Nitrosourea Bis-Chloronitrosourea Carmubris Carmustin Carmustinum FDA 0345 Gliadel N,N'-Bis(2-chloroethyl)-N-nitrosourea Nitrourean Nitrumon SK 27702 SRI 1720 WR-139021 6-O-Benzylguanine O(6)-Benzylguanine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kevin Cooper

Role: PRINCIPAL_INVESTIGATOR

Case Comprehensive Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Tacastacas JD, Chan DV, Carlson S, Gerson SL, Dowlati A, Fu P, Lu K, Groft S, Rosenjack J, Honda K, McCormick TS, Cooper KD. Evaluation of O6-Benzylguanine-Potentiated Topical Carmustine for Mycosis Fungoides: A Phase 1-2 Clinical Trial. JAMA Dermatol. 2017 May 1;153(5):413-420. doi: 10.1001/jamadermatol.2016.5793.

Reference Type DERIVED

PMID: 28199478 (View on PubMed)