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

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00003613
• Other study ID #: NCI-2012-03119
• Secondary ID: CWRU 6496U01CA06
• Status: Terminated
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: January 10, 2013
• Start date: April 1999

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• O6-benzylguanine
Given IV
• carmustine
Given topically

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes