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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Length of time from day of transplant until recurrence or relapse.
Lawrence G. Lum, MD, DSc
Barbara Ann Karmanos Cancer Institute
United States: Institutional Review Board
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|Sinai-Grace Hospital||Detroit, Michigan 48235|