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

PRIMARY OBJECTIVES:

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.

Inclusion criteria

• Patients with progressive HER2/neu overexpressing metastatic breast, ovarian, or non-small cell lung cancer not considered curable by conventional therapies, including trastuzumab

• 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

• Concurrent enrollment in other treatment studies
• 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)