RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer ductal breast carcinoma	Drug: autologous lymphocytes  Drug: interleukin-2  Drug: sargramostim  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy	Phase I Phase II

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Pulmonary:

• FEV_1, DLCO, and FVC at least 60% 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 except curatively treated squamous cell carcinoma in situ of the cervix or basal cell skin cancer

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

Rhode Island
      Roger Williams Medical Center, Providence,  Rhode Island,  02908-4735,  United States; Recruiting

Study chairs or principal investigators

Lawrence G. Lum, MD, DSc,  Study Chair,  Roger Williams Medical Center   

Study ID Numbers:  CDR0000069072; RWMC-0435146
Record last reviewed:  September 2004
Record first received:  December 7, 2001
ClinicalTrials.gov Identifier:  NCT00027807
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05