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

NCT ID: NCT00003613

Last Updated: 2013-01-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-04-30

Brief 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

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.

Conditions

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

O6-benzylguanine

Intervention Type: DRUG

Given IV

carmustine

Intervention Type: DRUG

Given topically

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

O6-benzylguanine

Given IV

Intervention Type: DRUG

carmustine

Given topically

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BG; BCNU; BiCNU; bis-chloronitrosourea

Eligibility 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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Cooper

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Locations

Case Western Reserve University

Cleveland, Ohio, United States

Countries

United States

References

Apisarnthanarax N, Wood GS, Stevens SR, Carlson S, Chan DV, Liu L, Szabo SK, Fu P, Gilliam AC, Gerson SL, Remick SC, Cooper KD. Phase I clinical trial of O6-benzylguanine and topical carmustine in the treatment of cutaneous T-cell lymphoma, mycosis fungoides type. Arch Dermatol. 2012 May;148(5):613-20. doi: 10.1001/archdermatol.2011.2797.

Reference Type: DERIVED

PMID: 22250189 (View on PubMed)

Other Identifiers

CWRU 6496

Identifier Type: -

Identifier Source: secondary_id

U01CA062502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-03119

Identifier Type: -

Identifier Source: org_study_id