This phase II trial studies the effect of DNA plasmid based vaccine (STEMVAC) in treating patients with patients with stage IB-III triple negative breast cancer. STEMVAC may wake up the immune system in patients who have had a diagnosis of triple negative breast cancer and have been treated. STEMVAC targets proteins that are expressed on breast cancer cells and works by boosting the immune system to recognize and destroy the invader cancer cell proteins that are causing the disease. The purpose of this trial is to test the immune system's response to STEMVAC.
OUTLINE: Patients receive STEMVAC vaccine with sargramostim intradermally (ID) every month for 3 months in the absence of disease progression or unacceptable toxicity. Patients then receive STEMVAC vaccine with sargramostim ID booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster vaccination. After completion of study treatment, patients are followed up at 28 days, and then annually for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
33
Given IV
Given ID
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Cellular immune response: incidence
Defined by the incidence of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT).
Time frame: At 1 month after 3rd vaccination
Cellular immune response: incidence
Defined by the incidence of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT).
Time frame: At 10 months after 3rd vaccination
Cellular immune response: magnitude
Defined by the magnitude of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT). The magnitude of immune response is defined as the sum of the corrected spots/well values calculated at each time point.
Time frame: At 1 month after 3rd vaccination
Cellular immune response: magnitude
Defined by the magnitude of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT). The magnitude of immune response is defined as the sum of the corrected spots/well values calculated at each time point.
Time frame: At 3 months after 3rd vaccination
Cellular immune response: magnitude
Defined by the magnitude of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT). The magnitude of immune response is defined as the sum of the corrected spots/well values calculated at each time point.
Time frame: At 9 months after 3rd vaccination
Cellular immune response: magnitude
Defined by the magnitude of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT). The magnitude of immune response is defined as the sum of the corrected spots/well values calculated at each time point.
Time frame: At 10 months after 3rd vaccination
Kinetics of the magnitude of antigen specific IFN-gamma ELISPOT counts
Will be assessed over time from pre to post immunization to determine if pre-existent immunity affects magnitude of response.
Time frame: 13 months
Incidence of adverse events
Safety and systemic toxicity will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 and monitoring of adverse events will be done per Food and Drug Administration and NCI guidelines.
Time frame: 1 month after last booster vaccine
Activation status and repertoire diversity of peripheral blood T-cells
The peripheral T cell repertoire diversity will be determined by high-throughput deoxyribonucleic acid (DNA) sequencing of the recombined V(D)J region of the T cell receptor beta-chain (TCRB) using the immunoSEQ platform (Adaptive Biotechnologies) on antigen-specific T-cells from a short-term in vitro culture. The activation, exhaustion and memory status of the peripheral T cells will be determined by flow cytometry using fluorochrome linked antibodies to PD-1, CD4, CD3, LAG3, CD137, CD8, KLGR1, CD44, CD69, CD62L and OX40. Transcription factors for Th1 (Tbet), Th2 (GATA3) and Treg (FOXP3) will also be evaluated. All results will be summarized using simple descriptive statistics.
Time frame: Prior to and after STEMVAC vaccination
Relapse free survival (RFS)
Will explore if adjuvant vaccination with STEMVAC improves relapse free survival as compared to historical controls. Local and distant recurrence at year 5 will be reported as proportion with confidence intervals, and RFS will be estimated using Kaplan-Meier method with the 5-year RFS rate estimated from the Kaplan-Meier estimate of the survival distribution along with a 95% confidence interval. Comparison of the local and distant recurrence and 5-year RFS against the historical control will be based on a binomial test.
Time frame: Up to 5 years
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