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Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)


- Determine whether the use of autologous peripheral blood stem cell transplantation
followed by immunotherapy with activated T cells in women with stage IV breast cancer
improves progression-free survival (PFS) compared to a reported mean PFS in patients
treated with second-line chemotherapy with matching inclusion criteria by published

- Determine if this regimen improves clinical response and overall survival.

- Perform sequential immune monitoring studies, including phenotyping, cytotoxic assays,
EliSpots for IFNγ, selected T-cell repertoire (Vβ analysis), HER2/new tetramer
analysis, and serum tumor markers.

- Test correlations between immune function tests and clinical endpoints.

OUTLINE: Patients are stratified according to tumor classification (chemosensitive vs

Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days followed by
peripheral blood mononuclear cell (PBMC) collection for PBSCT and generation of activated T
cells (ATC). The PBMC are treated ex vivo with monoclonal antibody OKT3 to form ATC. The ATC
are expanded for 12-14 days in interleukin-2 (IL-2).

Patients then receive high-dose chemotherapy. Patients with chemosensitive disease receive
cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on
days -4, -3, and -2. Patients with chemoresistant disease receive ifosfamide IV over 1 hour,
etoposide IV twice daily, and carboplatin IV over 1 hour on days -8 to -3. Patients undergo
autologous PBSC transplantation on day 0 or on both day 0 and day 1.

Patients then receive ATC IV over 15-20 minutes three times per week starting approximately
on day +1 for three weeks and then once weekly for at least 6 doses.

After completion of study therapy, patients are followed periodically for up to 2 years
after PBSC.

Inclusion Criteria


- Women with histologically documented metastatic carcinoma of the breast

- Bilateral disease allowed

- Concurrent intraductal or lobular carcinoma in situ allowed

- Measurable or evaluable recurrent metastatic disease (stage IV) documented by
radiograph, CT scan, nuclear medicine scan, or physical exam

- Biopsy of recurrent site(s) recommended but not required

- Nonmeasurable disease allowed if tumor or metastatic disease has been previously
removed or successfully treated

- 0 to 3+ HER2 amplification, as determined by FISH

- No clinical evidence of active brain metastases

- Patients with treated brain metastases (i.e., those who have received definitive
radiation, chemotherapy, and/or underwent surgery) and are stable are eligible

- Hormone receptor status:

- Estrogen or progesterone receptor positive or negative


- Menopausal status not specified

- Karnofsky performance status 70-100% OR ECOG performance status 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 greater than 8 g/dL

- Bilirubin less than 1.5 times normal

- AST, ALT, and alkaline phosphatase < 5 times upper normal

- Creatinine less than 1.8 mg/dL

- Creatinine clearance at least 60 mL/min

- BUN less than 1.5 times normal

- No myocardial infarction (MI) within the past year

- No history of MI (> 1 year ago) with current coronary symptoms requiring medication

- No current history of angina/coronary symptoms requiring medication

- No clinical evidence of congestive heart failure requiring medical management

- No significant congestive heart failure

- No other uncontrolled or significant cardiovascular disease

- Ejection fraction at least 45% at rest by MUGA

- Systolic BP < 130 mm Hg and diastolic BP < 80 mm Hg

- BP must be controlled to meet the standard by anti-hypertensive medications for
at least 7 days prior to the first infusion

- PFT-FEV_1 at least 50% predicted

- DLCO2 at least 50% predicted

- FVC at least 50% predicted

- No other malignancy within the past 3 years

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

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


- See Disease Characteristics

- Prior chemotherapy regimens allowed, including prior treatment on protocol

- Prior vaccine therapy on protocol WSU-2006-130 allowed

- More than 4 weeks to leukapheresis since prior hormonal therapy

- No radiation to the axial skeleton within 4 weeks of leukapheresis

- No concurrent hormonal therapy for breast cancer

- Hormones administered for non-disease-related condition (e.g. insulin for
diabetes) allowed

- Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed

Type of Study:


Study Design:

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

Outcome Measure:

Disease-free survival

Outcome Time Frame:

Length of time from day of transplant until recurrence or relapse.

Safety Issue:


Principal Investigator

Lawrence G. Lum, MD, DSc

Investigator Role:

Study Chair

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Institutional Review Board

Study ID:




Start Date:

August 2007

Completion Date:

Related Keywords:

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



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Sinai-Grace Hospital Detroit, Michigan  48235