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Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage II Cutaneous T-cell Non-Hodgkin Lymphoma

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Trial Information

Phase I/II Multicenter Clinical Trial of O6Benzylguanine and Topical Carmustine in the Treatment of Refractory Early-Stage (IA-IIA) Cutaneous T-Cell Lymphoma


I. To determine the CTCL response rate and safety of O6BG/BCNU when given biweekly as two
consecutive daily doses.


I. To determine the laboratory correlates of clinical response and drug efficacy based upon
the following surrogate marker studies:

- AGT activity in CTCL lesions will be examined to determine the effects of consecutive
day O6BG administration on the extent and duration of AGT depletion.

- Degree of induction of apoptosis and cell cycle arrest will be examined in the
malignant T-cell population of lymphomatous tissue and in the constitutive cells of the
skin to determine drug efficacy and toxicity through immunohistochemical techniques.

- MGMT gene mutations and changes in AGT expression will be examined as potential
mechanisms for O6BG resistance in non-responding patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of carmustine followed by a
phase II study.

Patients receive O6-benzylguanine (O6BG) IV over 1 hour and apply topical carmustine to the
total skin surface (excluding the lips, eyelids, and ulcerated lesions) 1 hour after
completing O6BG infusion on days 1-2. Treatment repeats every 2 weeks for up to 12 courses
in the absence of disease progression or unacceptable toxicity.

Tissue and blood samples may be collected for further analysis.

After completion of study treatment, patients are followed at 2 weeks.

Inclusion Criteria:

- Diagnosis of CTCL stages IA-IIA by histopathology and immunohistochemistry in
screening biopsies confirmed at Case Western Reserve University within 6 months of
enrollment; biopsies may be performed at the site of collaborating institutions and
shipped to UHC-CWRU

- 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 emolliation for at least 4 weeks, with the exception of
topical corticosteroids, which may be used up to 2 weeks before the trial start date

- Patients must have signed a consent form indicating the investigational nature of the
treatment and its potential side effects

- WBC > 4,000/ul

- ANC > 2000/ul

- Platelets > 100,000/ul

- Bilirubin < 1.5 mg/dL

- SGOT within normal range

- Creatinine =< 1.5 mg/dL

- Electrolytes normal

- Controlled (diet and insulin) diabetes is permitted

- Demonstration of clinically normal lung function based on history and physical
examination; patients with clinical evidence of pulmonary disease as determined by
the investigator should have baseline lung function tests performed with
demonstration of DLCO > 80%; a DLCO single breath, adjusted for hemoglobin, will be
utilized; we will not use DLCO/VA for inclusion or exclusion in this study

- Patients must have cutaneous disease that is amenable to biopsy and must be willing
to undergo several sequential biopsies

- Must have failed at least one conventional treatment for CTCL other than topical
corticosteroids; this includes phototherapy, topical mechlorethamine, topical or oral
bexarotene, radiation therapy, photopheresis, chemotherapy, and immunomodulatory
agents such as interferon and other retinoids

Exclusion Criteria:

- Patients who have received prior treatment with topical or systemic BCNU or other

- Patients with known central nervous system involvement or primary CNS malignancies

- 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 an active infection which requires hospitalization, or which may affect
the patient's safety if the patient was enrolled

- Patients with pulmonary disease as determined by history, physical examination, chest
X-ray, or pulse oximetry with DLCO < 80%

- CTCL patients with stage IIB-IVB disease

Type of Study:


Study Design:

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

Outcome Measure:

Overall response rate

Outcome Description:

Response rate and its confidence interval will be estimated based on binomial distribution theory. Statistical pair-wise comparisons of response rates between this phase I/II trial and the 30 and 40 mg (MTD) dose level cohorts from the Phase I trial using chi-square or Fisher's exact test will be performed.

Outcome Time Frame:

Up to 2 weeks after completion of study treatment

Safety Issue:


Principal Investigator

Kevin Cooper

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

Related Keywords:

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



Case Western Reserve University Cleveland, Ohio  44106