| Eligibility |
Inclusion Criteria:
- Histologically confirmed squamous CIN 3, or VIN 3 (usual type only)
- The subject is either surgically sterile, postmenopausal, or agrees to practice an
effective method of birth control as determined by the investigator (to be continued
throughout the study period), except that subjects with CIN 3 are not permitted to use
a cervical cap or diaphragm for contraception
- White blood cell > 2,500/ mcL (> 2.5 x 10^9/L)
- Absolute neutrophil count > 1,000/ microliter (> 1 x 10^9/L)
- Platelet count > 75,000/ mcL (> 75 x 10^9/L)
- Hemoglobin >= 8 g/dL (>= 80 g/L) (subjects who have received a transfusion or
erythropoietin up to one week prior to receiving the first dose of cyclophosphamide
are eligible for the study)
- International normalized ration (INR) or prothrombin time (PT) < 1.5 x ULN (upper
limit of normal)
- Activated partial thromboplastin time (aPTT) < 1.5 x ULN
- Serum creatinine < 1.5 x ULN
- Total bilirubin < 2.0 x ULN unless thought to be related to inherited bilirubin
conjugation disorder (ie Gilbert?s disease)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
- The subject is geographically accessible for ongoing follow-up and is committed to
comply with the designated visits
- The subject is capable of understanding and complying with the protocol and has signed
the enrollment informed consent form at screening
Exclusion Criteria:
- For subjects with cervical dysplasia: evidence of atypical glandular cells or
adenocarcinoma in situ (ACIS) based on cervical cytology, colposcopy or biopsy
- For subjects with either cervical or vulvar squamous dysplasia: evidence of
microinvasive squamous carcinoma based on cytology, colposcopy or biopsy
- Pregnancy or lactation
- Allergy to ciprofloxacin or other quinolones (because ciprofloxacin is used in
preparation of IRX-2)
- Allergy to indomethacin (a necessary component of the regimen) or to acetylsalicylic
acid (aspirin) due to likely allergy cross-reaction
- Aldara (imiquimod) for the topical treatment of lower genital tract warts or dysplasia
within 3 months of study enrollment
- Known to be positive for human immunodeficiency virus-1 (HIV-1) antibody, human
immunodeficiency virus-2 (HIV-2) antibody, hepatitis B surface antigen, or hepatitis C
virus antibody
- Known to have other immunodeficiency diseases, including cellular immunodeficiencies,
hypogammaglobulinemia, or dysgammaglobulinemia
- Immunotherapy (eg, interferons, tumor necrosis factor, interleukins) or biological
response modifiers (granulocyte-macrophage colony-stimulating factor, granulocyte
colony-stimulating factor, macrophage colony-stimulating factor) or any
investigational drug within 3 months of study enrollment
- Concurrent treatment with systemic corticosteroids at a dose of >= 5 mg/day of
prednisone (or equivalent)
- Subjects should not take aspirin (except for low-dose aspirin as prescribed for
vascular disease) or other non-prescribed, non-steroidal anti-inflammatory agents from
randomization to surgery
- An infectious process or any other significant illness such as an autoimmune disease
or advanced age that in the opinion of the investigator would compromise the subject?s
ability to mount an immune response
- Impaired hepatic, renal or hematological function, evidenced by:
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total
bilirubin >= 2 times upper limit of normal (ULN),
- Serum creatinine >= 2 times ULN, or
- Clinically significant active cardiovascular disease, including a history of
myocardial infarction within the past 6 months, heart failure as defined by New York
Heart Association classes III or IV, and/or blood pressure greater than 160/90 mm Hg
(1 repeat measure allowed no more than 5 minutes after the first measurement)
- History of severe allergic reaction to insect bites or stings, or to any biologic
pharmaceutical product, including compounds similar to the test article
- Any medical contraindications, allergies or previous therapy that would preclude
treatment with the components of the IRX-2 regimen, i.e., cyclophosphamide,
indomethacin, zinc-containing multivitamins or omeprazole
- Donation or loss of > 450 mL of blood or plasma within 30 days of randomization
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