SGN-00101 Immunotherapy in Treating Patients With Grade III Cervical Intraepithelial Neoplasia

OBJECTIVES:

Primary

- Determine the rate of regression at 4-7 months in patients with grade III cervical
intraepithelial neoplasia (CIN III) treated with SGN-00101 immunotherapy.

- Compare the rate of regression at 4-7 months with expected outcome in patients immunized
with this vaccine.

- Determine the toxic effects and recovery from possible toxic effects of this vaccine in
these patients.

Secondary

- Determine induction of cell-mediated immune responses against human papillomavirus (HPV)
E7 peptides before and after treatment in patients immunized with this vaccine

- Correlate regression of disease with enhanced immunologic responses in patients
immunized with this vaccine.

- Correlate seropositivity of HPV-16 virus-like particles (VLP16) with vaccine-induced
regression of CIN III in patients immunized with this vaccine.

- Determine the efficacy of this vaccine in patients whose CIN III is associated with
HPV-16 infection vs other HPV types.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.

All patients receive SGN-00101 subcutaneously once monthly on months 1-3 (for a total of 3
vaccinations) in the absence of disease progression or unacceptable toxicity.

- Group 1: Four months after the first vaccination, patients undergo therapeutic and
diagnostic loop electrosurgical excision procedure (LEEP) or core biopsy.

- Group 2: Six months after the first vaccination, patients undergo therapeutic and
diagnostic LEEP or core biopsy.

Patients in group 1 are followed at 12 months and patients in group 2 are followed at 14
months after the first vaccination.

PROJECTED ACCRUAL: A total of 66 patients (36 for group 1 and 30 for group 2) will be accrued
for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed grade III cervical intraepithelial neoplasia (CIN III) with
colposcopically visible cervical lesions

- No positive endocervical curettage or inadequate colposcopy at the time of initial
cervical biopsy

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- WBC at least 3,500/mm^3

- Lymphocyte count at least 500/mm^3

- Platelet count at least 150,000/mm^3

- Hemoglobin at least 10 g/dL

- No significant hematologic disease that is uncontrolled with standard therapy

Hepatic

- Bilirubin no greater than 2 mg/dL

- Liver enzymes no greater than 2.5 times normal

- No significant hepatic disease that is uncontrolled with standard therapy

Renal

- Creatinine no greater than 2 mg/dL

- No significant renal disease that is uncontrolled with standard therapy

Cardiovascular

- No significant cardiovascular disease that is uncontrolled with standard therapy

Pulmonary

- No significant respiratory disease that is uncontrolled with standard therapy

- No history of asthma

Immunologic

- HIV negative

- No clinical evidence of immunosuppression

- No autoimmune disease

- No history of allergic reactions attributed to compounds of similar chemical or
biological activity as those used in this study

- No history of a positive purified protein derivative (PPD) or Tine test

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Good health based upon the results of a medical history, physical examination, vital
signs, and laboratory profile

- No uncontrolled chronic disease

- Chronic disease requiring medication is allowed provided the patient is not
taking immunosuppressive drugs

- No significant endocrine (e.g., thyroid or diabetes), neurologic, gastrointestinal, or
dermatologic disease that is uncontrolled with standard therapy

- No other underlying or unstable disease that would be exacerbated by the study
treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior BCG vaccination

- No other concurrent vaccine therapy

Chemotherapy

- No concurrent chemotherapy

Endocrine therapy

- More than 30 days since prior oral or parenteral glucocorticoid steroid

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- More than 30 days since prior participation in another investigational study

- No concurrent cytotoxic therapy

- No other concurrent investigational agents

- No other concurrent investigational or commercial agents or therapies intended to
treat CIN