Vaccine Therapy in Treating Patients With Stage I, Stage II, or Stage III Non-small Cell Lung Cancer

Autologous Dendritic Cell Vaccines in Non-small Cell Lung Cancer (NSCLC)

RATIONALE: Vaccines made from a person's white blood cells and allogeneic tumor cells may make the body build an effective immune response to kill tumor cells.

PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with stage I, stage II, or stage III non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: autologous dendritic cell cancer vaccine

Detailed Description

OBJECTIVES:

• Determine the immunologic effects of adjuvant vaccine therapy comprising autologous dendritic cells loaded with allogeneic non-small cell lung cancer (NSCLC) cells in patients with unresectable stage IIIA or IIIB, or resected stage I-IIIB NSCLC.
• Determine the potential clinical efficacy of this vaccine in these patients.

OUTLINE: This is an open-label study. Patients are stratified according to type of prior primary therapy (surgical vs nonsurgical).

Patients undergo leukapheresis over 3-4 hours to harvest mononuclear cells for the production of dendritic cells (DC). DC are then pulsed with allogeneic non-small cell lung cancer cells to produce an autologous dendritic cell vaccine. Patients receive vaccine intradermally once a month for 2 months in the absence of disease recurrence or unacceptable toxicity.

Patients are followed monthly for 4 months, every 6 months for 2 years, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Markey Cancer Center at University of Kentucky Chandler Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

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

  • Meets 1 of the following stage criteria:

    • Completely resected stage I-IIIB disease

      • Underwent surgical resection > 4 weeks but ≤ 4 years ago
    • Unresectable stage IIIA or IIIB disease AND previously treated with definitive radiotherapy or chemotherapy > 6 weeks ago
  • Bronchoalveolar carcinomas allowed

• Clinically stable disease by chest x-ray or CT scan within the past 6 weeks

  • No progressive disease
• No malignant pleural or pericardial effusions

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Bilirubin ≤ 2.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• No known history of infectious hepatitis

Renal

• Creatinine ≤ 3 mg/dL
• Ionized calcium ≥ 0.9 mmol/L (may be replaced)

Cardiovascular

• No known New York Heart Association class III-IV congestive heart failure
• No hemodynamically significant valvular heart disease
• No myocardial infarction within the past 6 months
• No active angina pectoris
• No uncontrolled ventricular arrhythmia
• No stroke within the past year
• No known cerebrovascular disease
• No other significant cardiac disease by echocardiogram, stress test, or risk assessment by cardiologist (for patients suspected of cardiac disease by history or physical exam)

Immunologic

• No known HIV positivity
• No other immunosuppressive disorders, including chronic disorders

Other

• Not pregnant
• Negative pregnancy test
• Potassium ≥ 3.0 mEq/L (may be replaced)
• Able to tolerate modest blood volume and electrolyte shifts during leukapheresis
• No other malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed
• Other concurrent biologic therapy allowed

Chemotherapy

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy

• No concurrent steroids during and for 16 weeks after study treatment

Radiotherapy

• See Disease Characteristics
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Prior neoadjuvant or adjuvant therapy for surgically resected patients allowed
• No concurrent shorter courses of immunosuppressive medications during and for 16 weeks after study treatment
• No concurrent chronic immunosuppressive medications
• Concurrent cyclooxygenase-2 inhibitors allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous dendritic cell cancer vaccine; Open label nonrandomized	Biological: autologous dendritic cell cancer vaccine; Dendritic cells made from white blood cells obtained through out-patient leukapheresis procedure. Vaccine given by injection under the skin in the front, upper thigh. Two vaccine injections total, given one month a part.; Other Names: DC vaccine; autologous DC vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Showing Immunologic Response to Vaccine Within Six Months of Immunization	Antigen specific reaction is measured serially in blood of each participant prior to and through six months post-vaccine. Increase in levels of specific T cell activity from pre vaccine to post vaccine serve as primary measures of an individual's response to vaccine. The number (relative percent) of participants achieving immunologic response to vaccine within 6 month of immunization was the dominant metric of vaccine activity within the study population.	six months post vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Alive Five Years Post Vaccine	Documentation of radiographic surveillance for recurrence or progression for 5 years post-vaccine	five years post vaccine

Collaborators and Investigators

• Sponsor: Edward Hirschowitz
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Edward Hirschowitz, MD, Lucille P. Markey Cancer Center at University of Kentucky

Publications and helpful links

General Publications

• Hirschowitz EA, Foody T, Hidalgo GE, Yannelli JR. Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells. Lung Cancer. 2007 Sep;57(3):365-72. doi: 10.1016/j.lungcan.2007.04.002. Epub 2007 May 16.
• Hirschowitz EA, Foody T, Kryscio R, Dickson L, Sturgill J, Yannelli J. Autologous dendritic cell vaccines for non-small-cell lung cancer. J Clin Oncol. 2004 Jul 15;22(14):2808-15. doi: 10.1200/JCO.2004.01.074.
• Hirschowitz EA, Yannelli JR. Immunotherapy for lung cancer. Proc Am Thorac Soc. 2009 Apr 15;6(2):224-32. doi: 10.1513/pats.200806-048LC.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 7, 2005
• First Submitted That Met QC Criteria: February 7, 2005
• First Posted (Estimate): February 8, 2005

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage I non-small cell lung cancer; stage II non-small cell lung cancer; bronchoalveolar cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CDR0000410830; R21CA091624 (U.S. NIH Grant/Contract); UKMC-IRB-0391-F2R (Other Identifier: IRB); UKMC-CTRF-G-01-009 (Other Grant/Funding Number: Cancer Treatment Research Foundation)