Dendritic Cell Vaccine for High Risk Ovarian Cancer Patients

HLA-A2+ subjects with stage II-IV who have completed chemotherapy and are in clinical remission or patients with stage I-IV advanced ovarian cancer or primary serous peritoneal cancer in clinical remission post treatment for disease recurrence occurring after a progression-free interval of at least two years will be eligible. Patients will be evaluated by standard imaging techniques. Patients will be randomized to cyclophosphamide 300 mg/m2 (arm 2) or no cyclophosphamide (arm 1). All subjects will receive intradermal injections of DC on day 2 and on week 3, 6, and 9 (+ 3 days). All subjects will undergo leukocyte apheresis at study enrollment and at week 10, which is the end of active study intervention. All study arm 1 and 2 patients (without prior vaccination with the current season's vaccine) will receive a single dose of trivalent killed influenza vaccine, and a single dose of Prevnar pneumococcal vaccine on the day they receive their first intradermal injections of DC on day 2.

Inclusion criteria

• The following conditions must be met before a patient may be enrolled in the study.
• Patients age 18 years of age and older.

Disease Criteria. Patients will be eligible:

• If no clinical evidence of disease is present after diagnosis with stage III or
• IV disease and completion of primary surgery and chemotherapy, or, if no clinical evidence of disease is present after completion of chemotherapy for a disease recurrence diagnosed after a progression-free interval of at least 2 years, for patients of any initial stage.or primary peritoneal carcinoma.
• Complete clinical response = no evidence of tumor lesions shown by abdominal CT scan or MRI, chest Xray,and CA 125 level ≤ 35 UI/mL.
• Time from completion of Chemotherapy will be no more than 6 months from last dose from initial diagnoses.
• HLA-A2 positive (must be typed by molecular methods; all A2 alleles eligible).

Patients with adequate organ function as measured by:

• Hematopoietic: WBC at least 3000/mm3; platelets at least 100,000/mm3, hemoglobin at least 10.0 g/dL (may be transfused).
• Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be ≥50% or within the normal range of the institution. A cardiology clearance will be required for LV ejection fraction <50%.
• Hepatic: SGOT within 2x normal range and total bilirubin ≤ 2.0 mg/dL.
• Renal: Serum creatinine ≤2.0 mg/dL
• Adequate performance status > 80% (Karnofsky) or ECOG 0-2
• Written informed consent conforming to institutional guidelines.
• Life expectancy > 6 months and absence of co-existing medical problems which would preclude participation in the judgment of the principal investigator.

Exclusion criteria

• Any one of the following conditions eliminates a patient from participating in this protocol.
• Prior malignancy (except basal cell or squamous cell skin cancer) within the past five years.
• Presence of active Central Nervous System disease.
• Serious systemic disease.
• Active bacterial, viral or fungal infections.
• Chemotherapy, biologic therapy or radiation therapy less than 4 weeks prior to study entry.
• History of active autoimmunity or immunosuppression.
• Use of immunosuppressive drugs within 4 weeks prior to study entry or anticipated use of immunosuppressive agents.
• Patients with tumors of low malignant potential (borderline tumors) will not be eligible.
• Seropositivity for HIV, HTLV-1, or HTLV-2.
• Prior Influenza vaccination with the current vaccine will exclude patient from receiving protocol-specified influenza vaccine but will not exclude participation with the other aspects of the protocol. Each year's vaccine supply generally becomes available in October. Patients with a history of serious hypersensitivity to eggs, previous influenza vaccine or its components, will not receive influenza vaccine, but may continue to participate in other aspects of the protocol. Patients with a history of serious hypersensitivity to the Prevnar vaccine, its components, or diptheria toxoid will not receive the Prevnar vaccine, but may continue to participate in other aspects of the protocol.
• Pregnant or breast feeding subjects.