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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-01792 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE : Laboratory-treated T cells may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from HER2 peptides may help the body build an effective immune response to kill tumor cells that express HER2. Giving laboratory-treated T cells and cyclophosphamide after vaccine therapy may be an effective treatment for breast cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of ex vivo-expanded HER2-specific T cells when given together with cyclophosphamide after vaccine therapy in treating patients with HER2-positive stage IV breast cancer.
PRIMARY OBJECTIVES:
I. To evaluate the feasibility of expanding HER-2-specific effector T cells (TE) ex vivo from CD62L+ TCM and CD62L- TEM from patients immunized with a HER-2 peptide vaccine.
II. To evaluate the safety of infusing autologous ex vivo expanded HER-2-specific T cells into patients with advanced HER-2+ breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate the persistence, function, and phenotype of adoptively transferred HER-2-specific TE cells derived from TCM or TEM precursors.
II. To investigate the potential anti-tumor effects of therapy with ex vivo expanded HER-2-specific T cells in patients with advanced HER-2+ breast cancer.
OUTLINE : This is a dose-escalation study of ex vivo-expanded HER2-specific T cells.
VACCINE THERAPY: Patients receive HER2 peptide vaccine intradermally once weekly for 3 weeks.
CHEMOTHERAPY: Patients receive cyclophosphamide IV on day -1.
IMMUNOTHERAPY: Patients receive ex vivo-expanded HER2 specific T-cell IV over 30 minutes on days 1, 10, and 20.
After completion of study treatment, patients are followed up on days 28, 35, 49, 63 and then monthly thereafter for 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Experimental | VACCINE THERAPY: Patients receive HER2 peptide vaccine intradermally once weekly for 3 weeks. CHEMOTHERAPY: Patients receive cyclophosphamide IV on day -1. IMMUNOTHERAPY: Patients receive ex vivo-expanded HER2 specific T-cell IV over 30 minutes on days 1, 10, and 20. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HER-2/neu peptide vaccine | Biological | Given intradermally |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer | Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer will be defined as feasible if the minimum target expansion of HER-2-specific T cells is achieved in ≥2/3 expansions in ≥7/10 subjects. | After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy |
| Safety and systemic toxicity as assessed at regular time points by NCI common toxicity criteria (CTCAE v 4.0). Stopping rules for the study protect patients against therapy with a rate of severe toxicity of 20% or greater. | At week 1, 2, 3, post T-Cell infusion day 1, 10, 20, 28, 35, 49, 63, then every 3 months for a year. |
| Measure | Description | Time Frame |
|---|---|---|
| Extent to which to HER-2-specific T cell immunity can be boosted successfully with adoptive immunotherapy will be defined by quantitative assessment of HER-2-specific CD8+ T cells assessed by cytokine flow cytometry (CFC), Elispot, and tetramer staining | Post T-Cell-infusion on day 10, 20, 28, 35, 49, 63, then monthly for one year. | |
| Persistence of T cell immune augmentation in vivo after adoptive transfer of HER-2-specific T cells as assessed by presence of HER-2-specific central memory T cells and effector memory T cells |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lupe Salazar | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| cyclophosphamide | Drug | Given IV |
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| ex vivo-expanded HER2-specific T cells | Biological | Given IV |
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| laboratory biomarker analysis | Other | Correlative studies |
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| flow cytometry | Other | Correlative studies |
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| immunoenzyme technique | Other | Correlative studies |
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| Every month for 1 year following the last infusion |
| Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria | Day 63 post transplant |
| ID | Term |
|---|---|
| D018567 | Breast Neoplasms, Male |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D005434 | Flow Cytometry |
| D007124 | Immunoenzyme Techniques |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D007118 | Immunoassay |
| D007158 | Immunologic Techniques |
| D007150 | Immunohistochemistry |
| D015336 | Molecular Probe Techniques |
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