Overview
- To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA
and single IM TA-CIN immunization regimen
- To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
Eligibility
Inclusion Criteria:
- Female subjects age 25-70 years with confirmation of ASC-US, ASC-H, or LSIL by liquid-based cytology
- HIV uninfected
- Patients whose cytologic specimen is HPV16+ by Aptima HPV 16 18/45 Genotype Assay
- Body Mass Index ≤ 32 kg/m2
- Hepatitis B surface antigen negative
- Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV positive
- Patients who are able and willing to comply with all study procedures and voluntarily sign an informed consent form, and with anticipated availability for the planned follow-up period of one year
- Patients who are of childbearing potential agree to remain sexually abstinent, use methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 6 months.
- Patients must have adequate organ function at the time of enrollment as defined by the following parameters: white blood cell count >3,000/mcL; lymphocyte number >500/mcL; absolute neutrophil count >1,000/mcL; platelets >90,000/mcL; hemoglobin >9 g/dL; total bilirubin <3 X the institutional limit of normal; aspartate aminotransferase (AST [SGOT]) / alanine aminotransferase (ALT [SGPT]) <3 X the institutional limit of normal; creatinine <2.5X the institutional limit of normal.
- Histologic diagnosis of <CIN2 upon screening colposcopic examination with mandatory ECC, and cervical biopsy(ies) as clinically indicated.
Exclusion Criteria:
- Patients who are attempting pregnancy within 6 months, pregnant, or breastfeeding.
- Patients with immunodeficiency, or treatment with immunosuppressive medications
- Administration of any blood product within 3 months of enrollment.
- Administration of any licensed vaccine within 2 weeks of enrollment (4weeks for measles vaccine)
- Participation in a study with an investigational compound or device within 30 days of signing informed consent.
- History of seizures (unless seizure free for 5 years)
- Patients with positive serological test for human immunodeficiency virus (HIV).
- Previous cancer history within the past 5 years.
- Patients who have had chemotherapy, radiation, biological cancer therapy, or other investigational agents within 28 days prior to the first dose of study drug.
- Patients who have had surgery within 28 days, excluding minor procedures (dental work, skin biopsy, etc).
- Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing, or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
- Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies; patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids
- Previous cervical conization or LEEP procedure or previous total hysterectomy due to cervical lesions at enrollment.