Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine
NCT ID: NCT00228358
Last Updated: 2014-11-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
8 participants
INTERVENTIONAL
2003-06-30
Brief Summary
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Detailed Description
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I. To assess the feasibility of expanding HER2 specific T cells ex vivo for infusion into subjects who have advanced HER2 overexpressing cancer.
II. To assess the toxicity associated with infusing autologous HER2 specific T cells into patients using either a single dose of cyclophosphamide or ONTAK (denileukin diftitox) prior to T cell infusion.
SECONDARY OBJECTIVES:
I. To investigate to what extent HER2 specific T cell immunity can be boosted in individuals treated with a single dose of cyclophosphamide of ONTAK followed by infusion of autologous HER2 specific T cells.
II. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with HER2 overexpressing advanced-stage cancers.
III. To evaluate how long tumor antigen specific T cell immune augmentation persists in vivo after a single dose of cyclophosphamide or ONTAK followed by infusion of autologous HER2 specific T cells.
OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients are assigned to 1 of 2 treatment groups.
GROUP A: Patients receive low-dose cyclophosphamide intravenously (IV) on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
GROUP B: Patients receive ONTAK (denileukin diftitox) IV over 1 hour on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
After completion of study treatment, patients are followed periodically.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Group A (cellular infusions after cyclophosphamide)
Patients receive low-dose cyclophosphamide IV on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
ex vivo-expanded HER2-specific T cells
Laboratory-expanded T cells, given IV
cyclophosphamide
Given IV
flow cytometry
Intracellular cytokine staining (correlative study)
immunoenzyme technique
ELIspot assay (correlative study)
Group B (cellular infusions after ONTAK conditioning)
Patients receive denileukin diftitox IV over 1 hour on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
ex vivo-expanded HER2-specific T cells
Laboratory-expanded T cells, given IV
denileukin diftitox
Given IV
flow cytometry
Intracellular cytokine staining (correlative study)
immunoenzyme technique
ELIspot assay (correlative study)
Interventions
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ex vivo-expanded HER2-specific T cells
Laboratory-expanded T cells, given IV
cyclophosphamide
Given IV
denileukin diftitox
Given IV
flow cytometry
Intracellular cytokine staining (correlative study)
immunoenzyme technique
ELIspot assay (correlative study)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Extra-skeletal disease that can be accurately measured \>= 10 mm by standard imaging techniques that can include but not limited to computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI)
* Skeletal or bone-only disease which is measurable by Fludeoxyglucose F 18 (FDG) PET imaging will also be allowed
* Patients with ovarian cancer may have measurable disease; however, their only indication of progression may be an abnormal CA-125
* Patients must have documented HER-2/neu overexpression in their tumor (either primary or metastasis) as was required per the eligibility criteria of their original vaccination protocol
* Patients must have received HER2-specific vaccinations while enrolled on a HER2 vaccine protocol approved at the University of Washington Human Subjects Division
* Patients must have undergone leukapheresis after vaccination through a protocol approved at the University of Washington Human Subjects Division and have product stored for clinical use
* Subjects must have a Performance Status Score (Zubrod/Eastern Cooperative Oncology Group \[ECOG\] Scale) = 0 or 1
* Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy
* Patients on trastuzumab and/or lapatinib must have adequate cardiac function as demonstrated by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 90 days of eligibility determination
* Patients must be off all immunosuppressive treatments, and/or systemic steroid therapy, for at least 14 days prior to initiation of study treatment
* Patients must be off chemotherapy and trastuzumab for at least 1 week prior to the first infusion of T cells
* Men and women of reproductive ability must agree to contraceptive use during the study and for one month after the final T cell infusion
* Patients with a history of brain metastases must have a stable head imaging study within 30 days of enrollment
* White blood cells (WBC) \>= 3000/mm\^3
* Absolute neutrophil count (ANC) \>= 1000/mm\^3
* Hemoglobin (Hgb) \>= 10 mg/dl
* Platelets \>= 75,000mm\^3
* Serum creatinine =\< 2.0 mg/dl or creatinine clearance \> 60 ml/min
* Total bilirubin =\< 2.5 mg/dl
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =\< 3 times ULN
Exclusion Criteria
* Patients with any of the following cardiac conditions:
* Symptomatic restrictive cardiomyopathy
* Unstable angina within the last 4 months prior to enrollment
* New York Heart Association functional class III-IV heart failure on active treatment
* Patients with any clinically significant autoimmune disease uncontrolled with treatment
* Pregnant or breast-feeding women
* Known history of hypersensitivity to diphtheria toxin or interleukin (IL)-2 (only for subjects enrolled in Group B)
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
University of Washington
OTHER
Responsible Party
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Principal Investigators
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Mary Disis
Role: PRINCIPAL_INVESTIGATOR
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Locations
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Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Countries
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Other Identifiers
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NCI-2009-01547
Identifier Type: REGISTRY
Identifier Source: secondary_id
6223
Identifier Type: -
Identifier Source: org_study_id