Type I-Polarized Autologous Dendritic Cell Vaccine With Tumor Blood Vessel Antigen-Derived Peptides in Metastatic Breast Cancer Patients

PRIMARY OBJECTIVES:

I. Assess the safety of gemcitabine hydrochloride (GEM) + alpha-type-1 dendritic cell
(αDC1)-tumor blood vessel antigen (TBVA) vaccination (tumor blood vessel antigen
peptide-pulsed alpha-type-1 polarized dendritic cell vaccine).

II. Assess the clinical response of metastatic breast cancer (MBC) to GEM + αDC1-TBVA
vaccination.

III. Determine the clinical efficacy of GEM + αDC1-TBVA vaccination in generating T-helper 1
cell (Tc1) immunity.

IV. Correlate changes in myeloid-derived suppressor cells (MDSC) and regulatory T cells
(Tregs) with the generation of anti-TBVA T-cell immunity.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and
8. Treatment repeats every 21 days for 3 courses. Beginning 3, 7, or 10 days later, patients
receive tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell
vaccine intradermally (ID) followed by a second vaccination 7 days later. Courses may repeat
after at least 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Patients must be human leukocyte antigen (HLA)-A2+

- Histologically confirmed breast cancer

- Patients must have evidence of metastatic disease measurable by Response Evaluation
Criteria in Solid Tumors (RECIST) criteria or non-measurable lytic or mixed (lytic +
blastic) bone lesions in the absence of measurable disease; Note: Measurable lesions
include lytic or mixed (lytic + blastic) bone lesions, with an identifiable 10 mm soft
tissue component that meets the measurability criteria per RECIST

- There is no limit to the number of prior systemic treatment regimens

- Patients must have a life expectancy of > 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Prior GEM therapy is acceptable as long as the last dose was ≥ 3 months from
registration on this study

- Patients may have treated and stable brain metastases; they must be off steroids and
must have had stable brain metastases for at least 6 months

- White blood cell (WBC) > 3.0 x 10^9/L

- Platelets > 100 x 10^9/L

- Hemoglobin (Hgb) ≥ 10.0 gm/dl

- Creatinine < 1.5 mg/dl

- Bilirubin (total) < 2.0 ml/dl

- Aspartate aminotransferase (AST) < 5.0 x normal institutional limits

- Alkaline phosphatase < 2.5 upper limit of normal (ULN) (< 10 x ULN in presence of bone
metastases)

- Serum calcium ≤ 12 mg/dl

- International normalized ratio (INR) < 1.5, except for subjects receiving warfarin
therapy; for subjects who are receiving warfarin for prophylaxis or treatment of
thrombosis, INR values should be carefully monitored while patients are on study

- All patients must be informed of the investigational nature of this study and must
provide written informed consent in accordance with institutional and federal
guidelines; a copy of the informed consent document signed by the patient must be
given to the patient

- Patients must have a negative pregnancy test by urinalysis

- Use of an effective means of contraception (men and women) is mandated in subjects of
child-bearing potential; female subjects will be advised that they not become pregnant
for at least one month after completing participation in the study; avoiding sexual
activity is the only certain method to prevent pregnancy; however, if subjects choose
to be sexually active, they should use an appropriate "double barrier" method of birth
control (such as female use of a diaphragm, intrauterine device [IUD], or
contraceptive sponge, in addition to male use of a condom) or the use of prescribed
"birth control" pills, injections, or implants

Exclusion Criteria:

- HLA-A2 negative patients

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness

- Presence of bleeding diathesis

- Current treatment on another clinical trial

- Patients with organ allografts

- Pregnancy or breast-feeding; female patients must be surgically sterile or be
post-menopausal, or must agree to use effective contraception during the period of
therapy; all female patients with reproductive potential must have a negative
pregnancy test (serum or urine) prior to enrollment; male patients must be surgically
sterile or must agree to use effective contraception during the period of therapy; the
definition of effective contraception will be based on the judgment of the principal
investigator or a designated associate

- Other severe acute or chronic medical or psychiatric conditions, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the patient inappropriate for entry into
this study