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

January 10, 2013 updated by: National Cancer Institute (NCI)

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: O6-benzylguanine
Given IV
Other Names:
  • BG
Drug: carmustine
Given topically
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Kevin Cooper, Case Western Reserve University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1999

Primary Completion (Actual)

May 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 11, 2013

Last Update Submitted That Met QC Criteria

January 10, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-03119
  • U01CA062502 (U.S. NIH Grant/Contract)
  • CWRU 6496

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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