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Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

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ClinicalTrials.gov Identifier: NCT00791037
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary (Nora) Disis, University of Washington

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Interventions Biological: HER-2/neu peptide vaccine
Procedure: leukapheresis
Biological: ex vivo-expanded HER2-specific T cells
Drug: cyclophosphamide
Biological: sargramostim
Other: laboratory biomarker analysis
Enrollment 23
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Hide Arm/Group Description

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Period Title: Overall Study
Started 23
Primary Outcome 19
Skeletal or Bone-only Disease by FDG-PET 1
Completed 23
Not Completed 0
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo T Cell Expansion)
Hide Arm/Group Description

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
<=18 years
0
   0.0%
Between 18 and 65 years
22
  95.7%
>=65 years
1
   4.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
23
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
United States
22
  95.7%
Canada
1
   4.3%
1.Primary Outcome
Title Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Hide Description Patients are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, complete blood counts, urine analysis and physical exams. All adverse events for all systems are graded on a scale of 1-5 and attribution is assigned. There are DLT criteria. DLT is defined as any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding: fever, hypoxia, and urticaria) Thus, if a subject develops a Grade 3 toxicity (excluding those listed in Table 4) will be considered excessive toxicity and no further dose escalations will occur.
Time Frame Up to 4 months after first booster vaccine
Hide Outcome Measure Data
Hide Analysis Population Description
The infusion of escalating doses of HER2 specific T cells will be defined as safe if at least 75% of subjects are able to receive all 3 infusions without dose limiting toxicity (DLT)
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo-expanded T Cells)
Hide Arm/Group Description:

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: participants
0
2.Secondary Outcome
Title Proportion of Patients Whose T Cells Persist at a Level the Same or Greater as the Level After the Final T Cell Infusion and Subsequent Booster Immunizations as Assessed by IFN-gamma (IFN-g) ELISPOT
Hide Description [Not Specified]
Time Frame Up to 2 year following the last infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Vaccine Therapy)
Hide Arm/Group Description:

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
15
  78.9%
3.Secondary Outcome
Title Development of CD4+ and CD8+ Epitope Spreading
Hide Description As assessed by the development of immunity to epitopes within the HER2 protein to which the patient was not vaccinated as well as the development of immunity to other breast cancer related tumor antigens.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Hide Arm/Group Description:

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
12
  63.2%
4.Secondary Outcome
Title Response of Skeletal or Bone-only Disease by FDG-PET and According to European Organization for Research and Treatment for Cancer (EORTC)
Hide Description [Not Specified]
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Due to getting regulatory approvals we could only enroll 1 patient in this part of the protocol
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Hide Arm/Group Description:

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

Overall Number of Participants Analyzed 1
Measure Type: Count of Participants
Unit of Measure: Participants
1
 100.0%
Time Frame 2 years and 6 months (Vaccine 1 through follow-up)*
Adverse Event Reporting Description *The time between leukapheresis and first T cell infusion could vary due to patients being allowed to go back on treatment or scheduling conflicts.
 
Arm/Group Title Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Hide Arm/Group Description

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) 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 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 immunizations. 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 intervals.

HER-2/neu peptide vaccine: Given ID

leukapheresis: Undergo leukapheresis

ex vivo-expanded HER2-specific T cells: Given IV

cyclophosphamide: Given IV

sargramostim: Given ID

laboratory biomarker analysis: Correlative study

All-Cause Mortality
Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Affected / at Risk (%) # Events
Total   1/23 (4.35%)    
Vascular disorders   
Unrelated Pulmonary Embolus  1/23 (4.35%)  1
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Vaccine Therapy+ex Vivo Expanded T Cells)
Affected / at Risk (%) # Events
Total   23/23 (100.00%)    
Blood and lymphatic system disorders   
Anemia  13/23 (56.52%)  24
Axilla swelling/pain  1/23 (4.35%)  2
Blood Disorders - Not clinically significant  10/23 (43.48%)  30
Cardiac disorders   
Sinus tachycardia  1/23 (4.35%)  2
Cardiac arrhythmia  1/23 (4.35%)  1
Hypotension  1/23 (4.35%)  1
Ear and labyrinth disorders   
Tinnitus  1/23 (4.35%)  1
Eye disorders   
Ophthalmoplegia/diplopia (double vision)  1/23 (4.35%)  1
Gastrointestinal disorders   
Abdominal pain 1 [1]  3/23 (13.04%)  4
Constipation  8/23 (34.78%)  9
Diarrhea  7/23 (30.43%)  9
Nausea  11/23 (47.83%)  17
Vomiting  3/23 (13.04%)  6
General disorders   
Non caridac chest pain  4/23 (17.39%)  6
Fatigue (asthenia, lethargy, malaise)  13/23 (56.52%)  17
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  3/23 (13.04%)  5
Flu-like syndrome  7/23 (30.43%)  10
Injection site reaction  17/23 (73.91%)  52
Rigors/chills  5/23 (21.74%)  10
Vericella zoster  2/23 (8.70%)  2
Body aches  1/23 (4.35%)  1
Immune system disorders   
Allergic reaction/hypersensitivity (including drug fever)  2/23 (8.70%)  2
Infections and infestations   
Urinary tract infections  3/23 (13.04%)  5
Upper respiratory infection  3/23 (13.04%)  4
Lip infections 1 [2]  2/23 (8.70%)  3
Pharyngitis/Rhinitis  1/23 (4.35%)  1
Injury, poisoning and procedural complications   
Rash: Dermatitis associated with radiation  1/23 (4.35%)  1
Investigations   
Alkaline phos increased  2/23 (8.70%)  3
Alanine aminotransferase 1 [3]  3/23 (13.04%)  3
Aspartate aminotransferase increase 1 [4]  8/23 (34.78%)  9
White blood cell decreased  12/23 (52.17%)  17
Lymphopenia 1 [5]  13/23 (56.52%)  27
Neutrophil count decreased  5/23 (21.74%)  9
Platelets  3/23 (13.04%)  4
Weight loss  2/23 (8.70%)  2
Diaphoresis  1/23 (4.35%)  1
Creatinine  1/23 (4.35%)  1
Metabolism and nutrition disorders   
Anorexia  7/23 (30.43%)  8
Hypocalcemia  5/23 (21.74%)  5
Dehydration  1/23 (4.35%)  1
Hypoalbuminemia  10/23 (43.48%)  14
Hypokalemia  6/23 (26.09%)  6
Hyponatremia  12/23 (52.17%)  17
Electrolyte Abnormalities - Not Clinically Significant  10/23 (43.48%)  20
Musculoskeletal and connective tissue disorders   
Arthralgia 1 [6]  6/23 (26.09%)  6
Back pain  3/23 (13.04%)  6
Bone pain  6/23 (26.09%)  17
Myalgia  9/23 (39.13%)  10
Muscle pain  3/23 (13.04%)  3
Nervous system disorders   
Head/headache  12/23 (52.17%)  25
Dizziness  1/23 (4.35%)  1
sensory neuropathy  3/23 (13.04%)  3
Psychiatric disorders   
Insomnia  1/23 (4.35%)  1
Renal and urinary disorders   
Proteinuria  2/23 (8.70%)  2
Urinary frequency  1/23 (4.35%)  1
Non specific UA findings  11/23 (47.83%)  68
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  2/23 (8.70%)  3
Cough  7/23 (30.43%)  12
Skin and subcutaneous tissue disorders   
Dry skin  1/23 (4.35%)  1
Hair loss/alopecia (scalp or body)  1/23 (4.35%)  1
Hyperpigmentation  3/23 (13.04%)  4
Pruritis/itching  2/23 (8.70%)  2
Rash/desquamation  4/23 (17.39%)  5
Rash: acne/acneiform  4/23 (17.39%)  4
Erythema 1 [7]  1/23 (4.35%)  1
Vascular disorders   
Lymphedema  6/23 (26.09%)  7
Hot flashes/flushes  3/23 (13.04%)  3
Hypertension  1/23 (4.35%)  1
1
Term from vocabulary, CTCAE (3.0)
[1]
Pain
[2]
Herpes
[3]
Increased
[4]
Increase
[5]
lymphocyte count decrease
[6]
Arthralgia showed up various places: low back, R Hip, knee, joint
[7]
Left knee
All Other Adverse Events are reported regardless of attribution.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mary L. Disis
Organization: University of Washington
Phone: 206-543-8557
EMail: ndisis@u.washington.edu
Layout table for additonal information
Responsible Party: Mary (Nora) Disis, University of Washington
ClinicalTrials.gov Identifier: NCT00791037    
Other Study ID Numbers: 6658
NCI-2009-01591 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA129517 ( U.S. NIH Grant/Contract )
First Submitted: November 13, 2008
First Posted: November 14, 2008
Results First Submitted: October 13, 2016
Results First Posted: May 25, 2017
Last Update Posted: May 25, 2017