A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells After Second Line Chemotherapy in Women With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed metastatic breast cancer

- All histological types allowed

- Recurrent disease after first-line chemotherapy in the metastatic setting, as defined
by 1 of the following:

- No objective response after administration of ≥ 4 courses of first-line
chemotherapy

- Progression while receiving first-line chemotherapy without experiencing any
transient improvement

- Brief objective response to first-line chemotherapy with subsequent progression
while receiving the same therapy or within 12 months after the last dose of
therapy

- Patients who just started second line chemotherapy within 1 month allowed provided
there is no documented progressive disease on the second line chemotherapy

- HER2/neu-negative disease, defined as 0-2+ by IHC and/or FISH ratio (HER2 gene
signals to chromosome 17 signals) ≤ 2.2

- No HER2 overexpression by IHC or overamplification by FISH, as defined by any of
the following:

- 3+ IHC (uniform, intense membrane staining of > 30% of invasive tumor
cells)

- FISH result of > 6 HER2 gene copies per nucleus

- FISH ratio > 2.2

- Measurable or evaluable metastatic disease as documented by radiograph, CT scan,
PET/CT scan, MRI, bone scan, or physical exam

- At least 1 bidimensionally measurable lesion (that has not been irradiated) with
a minimum size in at least one diameter of ≥ 20 mm for liver lesions and ≥ 10 mm
for lung, skin, and lymph node metastases

- Biopsy of recurrent site(s) is not required

- No clinical evidence of active CNS metastases

- Patients with treated brain metastases (i.e., those who have received definitive
radiotherapy, chemotherapy, and/or surgical resection) are eligible

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Menopausal status not specified

- Karnofsky performance status 70-100%

- Life expectancy ≥ 3 months

- Granulocytes ≥ 1,000/mm³

- Platelet count ≥ 50,000/mm³

- Hemoglobin ≥ 8 g/dL

- BUN ≤ 1.5 times normal

- Serum creatinine < 1.8 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Bilirubin < 1.5 times normal

- ALT and AST < 5 times upper limit of normal (ULN)

- Alkaline phosphatase < 5 times ULN

- LVEF ≥ 45% at rest by MUGA or ECHO

- FEV_1, DLCO, and FVC ≥ 50% of predicted

- Negative pregnancy test

- No HIV positivity

- No myocardial infarction within the past year

- No current coronary symptoms requiring medications and/or evidence of depressed left
ventricular function (LVEF < 45% by MUGA or ECHO)

- No clinical evidence of congestive heart failure requiring medical management
(irrespective of MUGA/ECHO results)

- Patients whose systolic BP is consistently ≥ 140 mm Hg or diastolic BP is
consistently ≥ 80 mm Hg are eligible provided their BP is controlled by
antihypertensive medications for ≥ 7 days before the first activated T-cell infusion

- No other malignancy within the past 5 years except for basal cell skin carcinoma and
carcinoma in situ of the cervix

- No serious medical or psychiatric illness that would preclude informed consent or
intensive treatment

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 3 prior chemotherapy regimen for metastatic disease

- Prior taxanes, anthracyclines, or any other chemotherapy allowed

- No hormonal therapy within 2 weeks before leukapheresis

- No radiotherapy to the axial skeleton within 4 weeks before leukapheresis

- No concurrent steroids except those administered for adrenal failure, septic shock,
or pulmonary toxicity or hormones administered for nondisease-related conditions
(e.g., insulin for diabetes)