Ex Vivo-Expanded HER2-Specific T Cells and Cyclophosphamide After Vaccine Therapy in Treating Patients With HER2-Positive Stage IV Breast Cancer

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT01219907
First received: September 22, 2010
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
HER2-positive Breast Cancer
Male Breast Cancer
Stage IV Breast Cancer
Biological: HER-2/neu peptide vaccine
Drug: cyclophosphamide
Biological: ex vivo-expanded HER2-specific T cells
Other: laboratory biomarker analysis
Other: flow cytometry
Other: immunoenzyme technique
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 [ Time Frame: After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy ] [ Designated as safety issue: No ]
    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.

  • 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. [ Time Frame: At week 1, 2, 3, post T-Cell infusion day 1, 10, 20, 28, 35, 49, 63, then every 3 months for a year. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Post T-Cell-infusion on day 10, 20, 28, 35, 49, 63, then monthly for one year. ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Every month for 1 year following the last infusion ] [ Designated as safety issue: No ]
  • Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria [ Time Frame: Day 63 post transplant ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2012
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Biological: HER-2/neu peptide vaccine
Given intradermally
Other Name: HER-2
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Biological: ex vivo-expanded HER2-specific T cells
Given IV
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Other: immunoenzyme technique
Correlative studies
Other Name: immunoenzyme techniques

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01219907

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Salazar, Lupe, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT01219907     History of Changes
Other Study ID Numbers: 7266, NCI-2010-01792
Study First Received: September 22, 2010
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 23, 2014