SGN-00101 Vaccine in Treating Human Papillomavirus in Patients Who Have Abnormal Cervical Cells
SGN-00101 Vaccine in Treating Human Papillomavirus in Patients Who Have Abnormal Cervical Cells
This randomized phase II trial is studying how well SGN-00101 vaccine works compared to a
 placebo in treating human papillomavirus and preventing cervical cancer in patients with
 abnormal cervical cells. Vaccines, such as SGN-00101, may make the body build an immune
 response to kill human papillomavirus and abnormal cervical cells and may be effective in
 preventing cervical cancer
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