Biological Therapy in Treating Women With Stage IV Breast Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of armed activated T cells given in combination
with interleukin-2 and sargramostim (GM-CSF) in women with stage IV breast cancer.

- Determine the toxicity profile of this regimen in these patients.

- Determine the clinical response and overall and progression-free survival of patients
treated with this regimen.

OUTLINE: This is a dose-escalation study of armed activated T cells.

Patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMCs are treated
ex vivo with monoclonal antibody OKT3 to form armed activated T cells (ATC). The armed ATC
are expanded for 14 days in interleukin-2 (IL-2).

Patients receive armed ATC IV over 30 minutes twice weekly for 4 weeks. Patients also
receive IL-2 subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly
beginning 3 days before the first infusion of armed ATC and continuing until 7 days after
the last infusion of armed ATC.

Cohorts of 3-6 patients receive escalating doses of armed ATC until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional
patients are treated at that dose.

Patients are followed at 1, 2, and 5 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for the phase I portion of this
study and a total of 18-33 patients will be accrued for the phase II portion of this study
within 4-6 years.

PLEASE NOTE: THIS STUDY WAS INTENDED TO BE A PHASE I/II STUDY, BUT NEVER MOVED FORWARD TO
PHASE II. (4-22-09)

DISEASE CHARACTERISTICS:

Phase I:

- Histologically confirmed infiltrating ductal carcinoma of the breast

- Metastatic disease

- Clinically asymptomatic with non-life-threatening metastases allowed

- Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone
scan, or physical examination

- No measurable disease allowed if tumor or metastasis has been removed or
successfully treated prior to study

- No rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs
and liver)

- Stable or unstable disease for 3 months on hormonal therapy

- Stable or unstable disease for at least 1 month after chemotherapy

- No active brain metastases

- Brain metastases previously treated with definitive radiotherapy and/or surgical
resection allowed

- Hormone receptor status:

- Estrogen and progesterone receptor status known

Phase II:

- All Phase I criteria

- HER2/neu overexpression (2+ or 3+) by immunohistochemistry

- Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex:

- Female

Menopausal status:

- Not specified

Performance status:

- Karnofsky 70-100% OR

- ECOG 0-2

Life expectancy:

- At least 3 months

Hematopoietic:

- Granulocyte count at least 1,500/mm^3

- Platelet count at least 50,000/mm^3

- Hemoglobin at least 8 g/dL

Hepatic:

- Bilirubin less than 1.5 times normal

- SGOT less than 1.5 times normal

Renal:

- Creatinine no greater than 1.8 mg/dL

- Creatinine clearance at least 60 mL/min

- BUN no greater than 1.5 times normal

Cardiovascular:

- No myocardial infarction within the past year

- No prior myocardial infarction with coronary symptoms requiring medication and/or
depressed left ventricular function (LVEF less than 50% by MUGA)

- No angina or coronary symptoms requiring medication and/or with depressed left
ventricular function (LVEF less than 50% by MUGA)

- No congestive heart failure requiring medical management

- LVEF at least 50% at rest by MUGA

- No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 130 mm Hg or
diastolic BP ≥ 80 mm Hg)

Pulmonary:

- FEV1, DLCO, and FVC at least 50% predicted

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No other serious medical or psychiatric illness that would preclude study
participation

- No other prior or concurrent malignancy within the past 5 years except curatively
treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any
other curatively treated disease in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- Prior trastuzumab allowed for phase I

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

Endocrine therapy:

- See Disease Characteristics

- Concurrent hormonal therapy for breast cancer must continue during study

- No other concurrent hormonal therapy except steroids for adrenal failure, septic
shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions
(e.g., insulin for diabetes)

Radiotherapy:

- See Disease Characteristics

Surgery:

- See Disease Characteristics