Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Advanced Refractory or Recurrent Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI, Pharmaceutical / Industry	NCI-04-C-0049 NLGC-0101, NCT00075790

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

1. 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. (phase I, completed 10/06/09)
2. Determine tumor response rate in patients treated with this vaccine. (phase II)

Secondary

1. Determine the immunological response in patients treated with this vaccine. (phase II)
2. Determine the survival distribution and duration of response in patients treated with this vaccine. (phase II)

Entry Criteria

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
• Patients should have:
  • NSCLC sites that are accessible to needle, punch, or other limited biopsy
    • Sites may include skin and soft tissue metastases, adrenal gland metastases, or peripheral lymph nodes (supraclavicular, axillary, or inquinal)
  • A pulmonary lesion at low-risk for biopsy and/or complications defined as lesions >1.5 cm surrounded by aerated lung, pleural-based masses >1.5 cm and lesions not associated with a major pulmonary vessel, or other disease sites that may undergo biopsy with minimal discomfort and risk to the patient (these sites are optional)
• 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)

Prior/Concurrent Therapy:

Biologic therapy

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

Chemotherapy

• See Disease Characteristics
• Prior surgery, radiotherapy, immunotherapy, and/or chemotherapy regimens for NSCLC, including neoadjuvant and adjuvant treatment, allowed
  • 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

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 ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Absolute lymphocyte count ≥ 475/mm³

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
• Willing to undergo tumor core needle biopsy, punch or other similar biopsy pre-vaccination and again post-vaccination
• 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

Expected Enrollment

A total of 54 patients will be accrued for this study within 3-4 years.

Outcomes

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)
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)

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

Outline

This is a non-randomized, open-label, dose-escalation followed by a phase II study. (Phase I is closed to accrual as of 10/06/09)

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.

Some patients undergo tumor tissue biopsies at baseline and within 28 days of last vaccination for cellular immune response by IHC assays. Blood samples are also collected at baseline and periodically during study for immune response by ELISA, total immunophenotyping by FACS, and Western Blot.

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.

Morris JC, Janik JE, Vahanian N, et al.: A phase I study of antitumor vaccination using genetically modified tumor cells expressing (1,3) galactosyltransferase in patients with refractory or recurrent non-small cell lung cancer (NSCLC): preliminary results. [Abstract] American Society of Gene Therapy: 8th Annual Meeting, 1-5 June, 2005, St. Louis, MO. A-1133, 2005.

Morris JC, Vahanian N, Janik JE, et al.: Phase I study of an antitumor vaccination using α(1,3) galactosyltransferase expressing allogeneic tumor cells in patients (Pts) with refractory or recurrent non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 23 (Suppl 16): A-2586, 187s, 2005.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

John Morris, MD, Protocol chair		Ph: 301-402-2912 Email: jmorris@mail.nih.gov
Charles Joseph Link, MD, Protocol co-chair		Ph: 515-296-5555

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Contact Person	Ph:  888-NCI-1937

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title		A Phase I/II Study Of An Antitumor Vaccination Using α(1,3) Galactosyltransferase Expressing Allogeneic Tumor Cells In Patients With Refractory Or Recurrent Non-Small Cell Lung Cancer
Trial Start Date		2003-12-22
Trial Completion Date		2010-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00075790
Date Submitted to PDQ		2003-12-05
Information Last Verified		2009-06-03

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