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Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I/II)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

Thank you

Trial Information

Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I/II)


- 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.

Inclusion Criteria


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



- 18 and over


- Female

Menopausal status:

- Not specified

Performance status:

- Karnofsky 70-100% OR

- ECOG 0-2

Life expectancy:

- At least 3 months


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

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

- Hemoglobin at least 8 g/dL


- Bilirubin less than 1.5 times normal

- SGOT less than 1.5 times normal


- Creatinine no greater than 1.8 mg/dL

- Creatinine clearance at least 60 mL/min

- BUN no greater than 1.5 times normal


- 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)


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


- 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

- 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


Biologic therapy:

- See Disease Characteristics

- Prior trastuzumab allowed for phase I


- 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)


- See Disease Characteristics


- See Disease Characteristics

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

The dose at which dose-limiting toxicity occurs is defined as that dose at which 2 or more of 6 patients at that dose level have their infusions stopped due to toxicities or receive less than 80% of the planned dose.

Safety Issue:


Principal Investigator

Lawrence G. Lum, MD, DSc

Investigator Role:

Study Chair

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2001

Completion Date:

August 2012

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • ductal breast carcinoma
  • Breast Neoplasms



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201