Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

OUTLINE: This is a multicenter study.

- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]):
Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (HLA-A1) transfected
tumor cell vaccine intradermally (ID) in weeks 1, 3, and 5. Treatment repeats every 6
weeks for 2 courses. If no more than 1 of 6 patients experience a probable or
definitively treatment related adverse effect (i.e., grade 2 autoimmune or grade 3-4 of
any type), patients proceed to the phase II portion of the study. If 2 or more (out of
6) patients experience treatment related adverse effects the study stops.

- Phase II (randomized): Patients are stratified according to study site (University of
Miami Sylvester Comprehensive Cancer Center or Memorial Regional Hospital), type of
prior first-line treatment (platinum and taxane vs platinum and gemcitabine), and
presence of brain metastasis (yes vs no). Patients are randomized to 1 of 2 treatment
arms.

- Arm I: Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine
ID in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses.

- Arm II: Patients receive a placebo vaccine as in arm I. Patients undergo blood
sample collection periodically for correlative studies. Samples are analyzed for
cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural
killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell
1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β,
IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis
factor-alpha (TNF-α) via ELISA.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 4 years, and then once a year thereafter.

PROJECTED ACCRUAL: A total of 66 patients (6 patients for phase I and 60 patients for phase
II) will be accrued for this study.

INCLUSION CRITERIA

- Patients with stage IIIB (non-candidates for radiation) or stage IV pathologically
confirmed non-small cell carcinoma of the lung that completed 4-6 cycles of platinum
based first line chemotherapy and achieved complete response (CR), partial response
(PR) or stable disease.

- Last administration of chemotherapy occurred no later than 4 weeks prior to the
enrollment date.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

- Renal Requirements: The calculated creatinine clearance must be at least 50 ml/min.

- Pulmonary Function Requirements:

- All patients will undergo evaluation of pulmonary function prior to enrollment.

- Patients should have a Forced expiratory volume in 1 second (FEV1) more than 30%
of the predicted value and/or Diffusing capacity (DLCO) more than 30% of the
predicted value with a partial pressure of carbon dioxide (PCO2) < 45mm.

- Any patient enrolled in the protocol whose respiratory symptoms have experienced
marked deterioration not related to a known cause (e.g. pneumonia, congestive
heart failure (CHF) or pulmonary embolism (PE)) will have request pulmonary
function test (PFT) evaluation and if the above parameters are seen will be
excluded from the protocol.

- Age ≥ 18 years.

- Signed informed consent.

- Patients should have absolute neutrophil count (ANC) ≥ 1000/mm3; platelets (PLT) ≥
80,000/mm3.

EXCLUSION CRITERIA:

- Small cell carcinoma of the lung.

- Existing autoimmune disorders such as rheumatoid arthritis, systemic lupus
erythematosus, Sjogren's disease etc; colitis, inflammatory bowel disease or
pancreatitis within 10 years of study.

- Other active malignancies present within the past three years, except for basal and/or
squamous cell carcinoma(s) or in situ cervical cancer.

- Concomitant steroid or other immunosuppressive therapy.

- Active infection, or less than 7 days since therapy for acute infections.

- Pericardial effusion.

- Currently receiving chemotherapy for another condition (such as arthritis).

- Time elapsed greater than 4 weeks since last administration of first line chemotherapy
for NSCLC.

- Active or symptomatic cardiac disease such as congestive heart failure, angina
pectoris or recent myocardial infarction.

- Pregnant or lactating women (negative test for pregnancy required of women of
childbearing potential).

- Refusal in fertile men or women to use effective birth control measures during and for
six months after the completion of treatment on study.

- Known HIV infection

- Untreated or uncontrolled brain metastasis.

- Liver Enzymes greater than 3 times the institutional upper limit.