A Phase I Trial of CCL21 Gene Modified Dendritic Cells In Non-Small Cell Lung Cancer
- 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
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
Jay M. Lee, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|
|VA Greater Los Angeles||Los Angeles, California 90073|