Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Vaccine Therapy in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center Identifier:
First received: January 10, 2008
Last updated: September 8, 2014
Last verified: September 2014

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Condition Intervention Phase
Lung Cancer
Biological: autologous dendritic cell-adenovirus CCL21 vaccine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of CCL21 Gene Modified Dendritic Cells In Non-Small Cell Lung Cancer

Resource links provided by NLM:

Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Toxicity as measured by NCI Common Toxicity Criteria [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease status at days 28 and 56 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Immune response assessment by antigen-specific IFNγ ELISPOT assays on days 0, 28, and 56 [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: February 2009
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: experimental arm Biological: autologous dendritic cell-adenovirus CCL21 vaccine
Eligible patients will be assigned to a cohort and will receive intratumoral injections of Ad-CCL21-DC in conjunction with tumor sampling.

Detailed Description:



  • To determine the safety, toxicity, and maximum tolerated dose (MTD) of autologous dendritic cell-adenovirus CCL21 vaccine administered as an intratumoral injection in treating patients with stage IIIB, IV, or recurrent non-small cell lung cancer.


  • To determine the biologic and clinical responses to therapy.
  • To determine treatment-related toxicity using the NCI Common Toxicity Criteria.
  • To identify the MTD.
  • To monitor patients for evidence of autologous dendritic cell-adenovirus CCL21 vaccine-induced cytokines and antigen-specific immune responses.
  • To detect immune responses to tumor-associated antigens and vector.
  • To assess patients for objective signs of tumor regression (RECIST Criteria).

OUTLINE: This is a dose-escalation study of autologous dendritic cell-adenovirus CCL21 vaccine.

Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Adenovirus carrying the CCL21 gene is added to the dendritic cells to make the vaccine. Approximately 2 weeks after leukapheresis, patients receive an intratumoral injection of autologous dendritic cell-adenovirus CCL21 vaccine under CT-guidance or by bronchoscopy on days 0 and 7. Patients demonstrating a clinical response are eligible to receive a second round of gene transfer at their discretion and in consultation with the FDA.

Cohorts of 3 patients receive escalating doses of autologous dendritic cell-adenovirus CCL21 vaccine until the maximum tolerated dose (MTD) is determined. An additional 12 patients are treated at the MTD.

Patients undergo blood sample collection at baseline and then on days 0, 7, 14, 28, and 56 for safety and immunological studies. Blood samples are analyzed for mycoplasma by PCR; dendritic cell phenotype by flow cytometry; detection of adenovirus CCL21 by nested PCR; and adenoviral antibodies by ELISA. Patients also undergo tissue aspirate or biopsy on days 0 and 7 (during bronchoscopy or CT-guided procedure). Tissue samples are analyzed for immune-modulating cytokines (i.e., IFNγ, CXCL9, and CXCL10) by quantitative RT-PCR; detection of tumor infiltrating leukocytes by immunohistochemistry; CD83+ DC, CXCR3, CCR7, CCL21 and CD3+ T-cells, CD4, and CD8 by flow cytometry; determination of tumor expression of tumor-associated antigen by RT-PCR; and evaluation of immune modulation by ELISPOT assays.

After completion of study treatment, patients are followed periodically.


Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults over the age of 21 capable of giving informed consent
  • Pathologically confirmed non-small cell lung cancer (NSCLC)
  • Stage IIIB, IV, or recurrent disease
  • Progressive disease despite one or more prior chemotherapy regimens as standard of care OR patient refuses standard chemotherapy
  • Measurable metastatic disease by RECIST guidelines
  • Patients with a major endobronchial lesion in the segmental, lobar, or mainstem bronchus with complete obstruction of the airway may be eligible for bronchoscopic injection provided there is no evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 L)
  • Patients with an endobronchial lesion in the segmental bronchus with variable stenosis (not completely obstructed) and not amenable to standard palliative airway treatments (i.e., laser and stenting) may be eligible for bronchoscopic injection if there is no evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 liters)
  • Patients with bullous disease may undergo CT-guided transthoracic injection provided the targeted tumor has an intended needle path without crossing bullae
  • ECOG performance status 0-2
  • BUN ≤ 40 OR serum creatinine ≤ 2
  • Serum total bilirubin ≤ 1.5 OR serum transaminases ≤ 2.5 times upper limit of normal (ULN)
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • More than 14 days since prior acute therapy for viral, bacterial, or fungal infections
  • More than 30 days since prior and no concurrent corticosteroids
  • More than 30 days since prior radiotherapy, chemotherapy, or noncytotoxic investigational agents

Exclusion Criteria:

  • active CNS metastasis (i.e., progression of CNS disease during the past 30 days without intervention)
  • evidence of coagulopathy, defined as PT and/or PTT ≤ 1.5 times ULN OR platelets ≥ 100,000/mm^3
  • evidence of leukoplakia, defined as absolute neutrophil count ≥ 1,500/mm^3
  • evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 L)
  • NYHA class III-IV cardiac disease within the past year
  • myocardial infarction within the past year
  • comorbid disease or medical condition that would impair the ability of the patient to receive or comply with the study protocol
  • acute viral, bacterial, or fungal infection that requires specific therapy
  • HIV positivity
  • hypersensitivity to any reagents used in the study
  • signs or symptoms of acute adenoviral infection (i.e., conjunctivitis or documented adenoviral upper respiratory infection)
  • prior or concurrent evidence of autoimmune disease
  • pregnant or nursing
  • prior organ allograft
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00601094

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
VA Greater Los Angeles
Los Angeles, California, United States, 90073
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Study Chair: Jay M. Lee, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center Identifier: NCT00601094     History of Changes
Other Study ID Numbers: 03-06-008, P30CA016042, UCLA-NCI-7888
Study First Received: January 10, 2008
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms processed this record on February 25, 2015