Expired Study
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Seattle, Washington 98109


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.


Study summary:

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.


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


Study is Available At:


Original ID:

7266


NCT ID:

NCT01219907


Secondary ID:

NCI-2010-01792


Study Acronym:


Brief Title:

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


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


Overall Status:

Withdrawn


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Washington


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

0


Enrollment Type:

Actual


Overall Contact Information

Official Name:Lupe Salazar
Principal Investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Dates

Start Date:June 2012
Primary Completion Date:June 2014
Primary Completion Type:Anticipated
Verification Date:May 2013
Last Changed Date:May 15, 2013
First Received Date:September 22, 2010

Study Outcomes

Outcome Type:Primary 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
Time Frame:After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy
Safety Issues:False
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 ex
Outcome Type:Primary Outcome
Measure: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.
Safety Issues:True
Outcome Type:Secondary Outcome
Measure: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.
Safety Issues:False
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria
Time Frame:Day 63 post transplant
Safety Issues:False

Study Interventions

Intervention Type:Biological
Name:HER-2/neu peptide vaccine
Description:Given intradermally
Arm Name:Arm I
Other Name:HER-2
Intervention Type:Drug
Name:cyclophosphamide
Description:Given IV
Arm Name:Arm I
Other Name:CPM
Intervention Type:Biological
Name:ex vivo-expanded HER2-specific T cells
Description:Given IV
Arm Name:Arm I
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Arm I
Intervention Type:Other
Name:flow cytometry
Description:Correlative studies
Arm Name:Arm I
Intervention Type:Other
Name:immunoenzyme technique
Description:Correlative studies
Arm Name:Arm I
Other Name:immunoenzyme techniques

Study Arms

Study Arm Type:Experimental
Arm Name:Arm I
Description: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.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Washington
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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