SGN-00101 Vaccine in Treating Human Papillomavirus in Patients Who Have Abnormal Cervical Cells

PRIMARY OBJECTIVES:

I. Compare the effectiveness of SGN-00101 vaccine vs placebo in reducing the human papillomavirus (HPV)-16 viral load in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) of the cervix with persistent HPV-16 infection who are at increased risk for developing a high-grade squamous intraepithelial lesion or invasive cervical cancer.

II. Compare the natural history of HPV-16 viral load in patients treated with these regimens.

III. Compare the effect of HPV-16 variants on viral load response in patients treated with these regimens.

IV. Compare the relative effectiveness of these regimens on the regression of cervical cellular atypias (based on Pap test results), in terms of the regression of cytologic findings of LSIL and ASCUS to normal findings and resolution or regression of colposcopically defined cervicovaginal lesions, in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive SGN-00101 vaccine subcutaneously (SC) on day 1 of weeks 1, 4, and 8 for a maximum of 3 injections in the absence of unacceptable toxicity or the development of an invasive malignancy or serious illness.

ARM II: Patients receive placebo vaccine SC on day 1 of weeks 1, 4, and 8 for a maximum of 3 injections in the absence of unacceptable toxicity or the development of an invasive malignancy or serious illness.

Patients are followed at 12, 24, and 52 weeks after the last vaccination.

Inclusion criteria

• Meets criteria for 1 of the following groups:

• Prospective group, meeting the following criteria:

• Evidence of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) by Pap test
• Human papillomavirus (HPV)-16-positive by polymerase chain reaction (PCR) and PGMY09/PGMY11 oligonucleotide primers viral load assay
• Medical records-based group, meeting the following criteria:

• Medical-record evidence of ASCUS or LSIL by Pap test within the past 6-12 months
• Meets 1 of the following criteria:

• Liquid-cytology findings of ASCUS or LSIL
• Colposcopic evidence of a LSIL by the Reid Index score of 1-5
• Historically persistent HPV-16-infection by PCR and HPV reverse transcription (RT)-PCR
• No evidence of high-grade squamous intraepithelial lesions (HSIL) by colposcopy (Reid Index ≥ 6)
• Reports no sex partner change since last index Pap screening test
• Specimen-based group, meeting the following criteria:

• Medical-record evidence of ASCUS or LSIL by Pap test within the past 6-12 months

• Liquid-based cytology specimen available
• Meets 1 of the following criteria:

• Liquid-cytology findings of ASCUS or LSIL
• Colposcopic evidence of a LSIL by the Reid Index score of 1-5
• Historically persistent HPV-16-infection by PCR and, where measurable, HPV RT-PCR showing no greater than 3-fold reduction over the index liquid-cytology specimen
• No evidence of HSIL by colposcopy (Reid Index ≥ 6)
• Menstrual period occurred at least once within the past 52 weeks
• No HSIL by Pap test within the past year
• Performance status - ECOG 0
• No severe or unstable coagulation
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative
• No angina
• No heart failure
• No other cardiac condition
• No respiratory condition
• No asthma
• No immunological disorders (e.g., lupus, diabetes, multiple sclerosis, or myasthenia gravis)
• Not immunocompromised, suggestive of severe immune deficiency
• HIV negative
• No AIDS
• No active infection, defined as fever > 100° F
• No syphilis
• No severe allergic reactions (anaphylactic response) to drugs or any other allergen
• No history of allergy to any vaccine constituents, including cell- or tissue-system elements used to prepare the vaccine (e.g., bread products, yeast, or recombinant DNA technology using yeast systems)
• Must agree to use effective form of contraception throughout vaccination period
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during vaccination period and for 5 months after study treatment
• No sexual intercourse within 48 hours of virus specimen collection during study visits
• No objects (e.g., tampons, douche, suppositories, fingers, or toes) within the vagina or rectum within 48 hours of virus specimen collection during study visits
• No prior malignancy except nonmelanoma skin cancer
• No medical or psychiatric illness than would preclude study participation or compliance
• No other disorders requiring medical intervention that would preclude study participation
• No prior HPV vaccine
• More than 30 days since prior investigational vaccine
• More than 30 days since prior systemic steroid therapy
• No prior splenectomy
• More than 30 days since prior investigational drug
• More than 72 hours since prior antibiotic therapy for active infection