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

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:

MedlinePlus related topics: Lymphoma

Drug Information available for: Carmustine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Cutaneous T-cell Lymphoma

U.S. FDA Resources

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 (Adult, Senior)
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Kevin Cooper	Case Western Reserve University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


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 Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders	Immune System Diseases Carmustine O(6)-benzylguanine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016