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Phase I Study of Adoptive T-Cell Therapy With HER-2/Neu (HER-2)-Specific Memory CD8+ T Lymphocytes Obtained Following In Vivo Priming With a Peptide Vaccine in Patients With Advanced Stage HER-2-Positive Breast Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
HER2-positive Breast Cancer, Male Breast Cancer, Stage IV Breast Cancer

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Trial Information

Phase I Study of Adoptive T-Cell Therapy With HER-2/Neu (HER-2)-Specific Memory CD8+ T Lymphocytes Obtained Following In Vivo Priming With a Peptide Vaccine in Patients With Advanced Stage HER-2-Positive 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.


Inclusion Criteria:



- Patients with HER-2+ Stage IV breast cancer that have been maximally treated and not
in a complete remission

- Subjects must be > 18 years old

- Extra skeletal disease that can be accurately measured in at least one dimension as
>= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan

- Skeletal or bone-only disease that is measurable by FDG PET imaging will also be
allowed

- Patients can be receiving trastuzumab and/or hormonal therapy and/or bisphosphonates

- HER2 overexpression in the primary tumor or metastasis by IHC of 2+ or 3+, or
documented gene amplification by FISH analysis; if over expression is 2+ by IHC,
patients must have HER2 gene amplification documented by FISH

- Performance Status Score (ECOG/Zubrod Scale) must be =< 2

- Patients must be off all immunosuppressive treatments such as chemotherapy or
systemic steroid therapy a minimum of 3 weeks prior to initiation of study (i.e.
first vaccination)

- Patients on trastuzumab must have a baseline LVEF measured by MUGA or echocardiogram
>= the lower limit of normal for the facility within 3 months of enrollment to study

- Subjects must be HLA-A2 (HLA A*0201) positive

- ANC >= 1000/mm^3

- Hgb >= 10 mg/dl

- Platelet count >= 75,000/mm^3

- Men and women of reproductive ability must agree to use contraceptives during the
entire study period

Exclusion Criteria:

- Serum creatinine > 2.0 mg/dl

- Serum bilirubin > 2.5 times the upper limit of normal

- Contraindication to receiving GM-CSF based vaccine products

- New York Heart Association functional class III-IV heart failure, symptomatic
pericardial effusion, or unstable angina

- History of disorders associated with immunosuppression such as HIV

- Pregnant or breast-feeding women

- ANC < 1000/mm^3

- Hgb < 10 mg/dl

- Platelet count < 75,000/mm^3

- Active brain metastasis

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy

Safety Issue:

No

Principal Investigator

Lupe Salazar

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

7266

NCT ID:

NCT01219907

Start Date:

June 2012

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male

Name

Location
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109