Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003613
First received: November 1, 1999
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of O6 Benzylguanine and BCNU in Cutaneous T-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percent decrease of AGT in CTCL skin lesions, obtained from tissue samples [ Time Frame: Baseline to 6 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 20
Study Start Date: April 1999
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: BG
Drug: carmustine
Given topically
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003613

Locations
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin Cooper Case Western Reserve University
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003613     History of Changes
Other Study ID Numbers: NCI-2012-03119, CWRU 6496, U01CA062502
Study First Received: November 1, 1999
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Carmustine
O(6)-benzylguanine
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014