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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
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.
Lawrence G. Lum, MD, DSc
Barbara Ann Karmanos Cancer Institute
United States: Food and Drug Administration
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|