Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
18 Years
N/A
Female
Breast Cancer
Trial Information
Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
OBJECTIVES:
- 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
trials.
- 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
chemoresistant).
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
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
participation
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior chemotherapy regimens allowed, including prior treatment on protocol
WSU-2006-130
- 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:
Interventional
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:
No
Principal Investigator
Lawrence G. Lum, MD, DSc
Investigator Role:
Study Chair
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Institutional Review Board
Study ID:
CDR0000068707
NCT ID:
NCT00020722
Start Date:
August 2007
Completion Date:
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- recurrent breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| Sinai-Grace Hospital | Detroit, Michigan 48235 |
