Phase I/II Study of Adoptive T Cell Therapy Following In Vivo Priming With a HER-2/Neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine in Patients With Advanced Stage HER2 Overexpressing Breast Cancer
I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into
patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.
I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated
in individuals after infusion of HER2 specific T cells.
II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer
of HER2 specific T cells and subsequent booster immunizations.
III. To determine the development of cluster of differentiation (CD)4+ and CD8+ epitope
spreading after adoptive transfer of HER2 specific T cells.
I. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with
advanced HER2+ breast cancer.
II. To determine whether indium-labeled HER-2 specific T-cells traffic to sites of
metastatic disease once adoptively transferred using SPECT or SPECT-CT imaging.
III. To assess whether adoptively transferred HER-2 specific T-cells induce acute
inflammation at metastatic sites of disease by assessing the development of tumor
inflammation after the second or third infusion of cells using PET-CT imaging.
OUTLINE: This is a phase I/II, dose-escalation study of ex vivo-expanded HER2-specific
autologous T cells.
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally
(ID) on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to
isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide intravenously (IV) once on day -1 and autologous ex
vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10
days for up to three treatments. Patients receive a booster HER2/neu peptide vaccine 1 month
after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month
While on the study, patients may continue their standard-of-care (non-research) treatment
with trastuzumab and/or lapatinib IV weekly or every 3 weeks, except for 7 days before the
cyclophosphamide dose, treatment 1 and treatment 2 and at least 7 days after receiving the
second T cell vaccine. (Trastuzumab and lapatinib are not required or provided in this
Before the third T cell treatment of HER2 specific T-cells we will label a small sample of
the patient's T-cells with indium-111. Prior to the final infusion of T-cells, patients
will have FDG PET-CT performed. This scan will be repeated 48 hours after T-cell infusion.
In addition, patients would then undergo SPECT or SPECT-CT imaging at 4, 24, 48, and 72
hours (+/- 3 hours) after labeled cells have been infused.
After completion of study treatment, patients are followed up every 3 months for 1 year,
every 4 months for the following year, and then twice a year thereafter. This consists of
blood collection and contact with patients physician.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and systemic toxicity of infusing HER2-specific T cells as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Defined as safe if at least 75% of patients are able to receive all 3 infusions without dose-limiting toxicity (DLT), any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding constitutional, pulmonary, or dermatology/skin categories) or any incidence of Grade 4 toxicity (excluding reversible Grade 4 blood/bone marrow category after cyclophosphamide).
Up to 4 months after first booster vaccine
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|