Clinical trial NCT00003613: O6-benzylguanine and Carmustine in Treating Patients With Stage IA-IIA Cutaneous T-cell Lymphoma
Official title: Phase I Trial of O6 Benzylguanine and BCNU in Cutaneous T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent decrease of AGT in CTCL skin lesions, obtained from tissue samples
timeFrame: Baseline to 6 weeks
measure: MTD of carmustine estimated as the dose level which is one level below where >= 2 DLT are observed
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
Study officials:
affiliation: Case Western Reserve University
name: Kevin Cooper
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.