• Adverse effects, dose-limiting toxicity, and maximum tolerated dose as measured by CTCAE v.3 and RECIST criteria pre-treatment, during study treatment, and 6 months after completion of study treatment (phase I) [ Designated as safety issue: Yes ]
  
• Tumor response rate as measured by CTCAE v.3 and RECIST criteria pre-treatment, during study treatment, and 6 months after completion of study treatment (phase II) [ Designated as safety issue: No ]
  

• Immunological response as measured by an assay of serum anti-alpha-gal titers and enzyme-linked immunospot assay for interferon-gamma and interleukin-5 pre-treatment and at 6 months after completion of study treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the side effects, dose-limiting toxicity, and maximum tolerated dose of vaccination comprising α-1,3-galactosyltransferase-expressing allogeneic tumor cells (HyperAcute™ Lung Cancer Vaccine) in patients with advanced refractory or recurrent non-small cell lung cancer.
• Determine tumor response rate in patients treated with this vaccine.

Secondary

• Determine the immunological response in patients treated with this vaccine.
• Determine the survival distribution and duration of response in patients treated with this vaccine.

OUTLINE: This is a non-randomized, open-label, dose-escalation study.

Patients receive vaccination comprising α-1,3-galactosyltransferase-expressing allogeneic tumor cells (HyperAcute™ Lung Cancer Vaccine [HAL]) intradermally on days 1, 29, 57, and 85 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of HAL vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 6 patients receive treatment at the MTD.

Quality of life is assessed at baseline; days 29, 57, 85, 99, and 127; and then every 2 months for 1 year.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then annually for 15 years.

PROJECTED ACCRUAL: A total of 52 patients (6-24 for phase I and 7-28 for phase II) will be accrued for this study within 3-4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC)

  • The following cellular subtypes are eligible:

    • Bronchoalveolar (papillary) carcinoma
    • Squamous cell (epidermoid)
    • Adenocarcinoma
    • Large cell anaplastic

  • Must meet criteria for 1 of the following stages:

    • Stage IV (any T, any N, M1)
    • Metastatic
    • Progressive or recurrent
• Failed at least 1 prior chemotherapy regimen OR refused chemotherapy for NSCLC
• Measurable or nonmeasurable disease
• No mixed NSCLC and small cell lung carcinoma or variant large and small cell lung carcinoma
• No active CNS metastases or carcinomatous meningitis
• Ineligible for other curative intent treatment (e.g., surgical resection)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 4 months

Hematopoietic

• Hemoglobin ≥ 10.0 g/dL
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Absolute lymphocyte count ≥ 475/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• Albumin ≥ 3.0 g/dL
• Hepatitis B and C negative
• No liver cirrhosis

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min
• No hypercalcemia > 2.9 mmol/L that is unresponsive to standard therapy (e.g., IV hydration, diuretics, calcitonin, and/or bisphosphonate therapy)

Cardiovascular

• No significant or uncontrolled congestive heart failure
• No myocardial infarction within the past 6 months
• No significant ventricular arrhythmias within the past 6 months

Pulmonary

• No significant pulmonary dysfunction
• A history of asthma or mild active asthma is allowed

Immunologic

• HIV negative
• No active infection or unexplained fever (i.e., temperature > 38.1°C)
• No autoimmune disease (e.g., systemic lupus erythematosus or active rheumatoid arthritis)
• No known allergy to any component of the study drug or cell lines from which it was derived

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation
• No other malignancy within the past 5 years except malignancies for which the probability of recurrence is less than 5%, curatively treated squamous cell or basal cell skin cancer, or carcinoma in situ of the cervix
• No other serious medical condition that would limit life expectancy to less than 2 years
• No other medical or psychiatric condition (e.g., untreated schizophrenia or other significant cognitive impairment) that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy
• At least 4 weeks since prior biological or targeted therapy

Chemotherapy

• See Disease Characteristics

• No more than 1 prior different chemotherapy or immunotherapy regimen for NSCLC, including neoadjuvant and adjuvant treatment

  • Preoperative neoadjuvant and postoperative (within 12 weeks after surgery) adjuvant chemotherapy with the same agent is considered 1 prior regimen
  • Gefitinib, erlotinib, monoclonal antibodies, or other small molecule or targeted therapies will be considered as prior chemotherapy or immunotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• No concurrent systemic corticosteroids

  • Concurrent inhaled or topical corticosteroids are allowed
• No concurrent replacement therapy for hypoadrenalism

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• No prior organ transplantation
• At least 4 weeks since prior major surgery

Other

• Recovered from all prior therapy (except alopecia and fatigue)
• More than 1 week since prior antibiotics
• No concurrent tacrolimus
• No other concurrent immunosuppressive therapy