Biological Therapy in Treating Women With Stage IV Breast Cancer
RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.
Biological: therapeutic autologous lymphocytes
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I/II)|
- Maximum tolerated dose [ 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. ] [ Designated as safety issue: Yes ]
- Toxicity profile [ Time Frame: Months 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: Yes ]
- Clinical responses [ Time Frame: Months: 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: No ]
- Overall survival and progression-free survival [ Time Frame: The interval from the beginning of immunotherapy to the time of death or for progression free survival it is defined as the interval from the beginning of immunotherapy to progression ] [ Designated as safety issue: No ]
- Immune changes [ Time Frame: 1 (+ 7 days), 2 (+ 7 days), 5 months (+ 7 days), then every 6months (+ 7 days) (immune evaluations will also be performed after the 4th and 8th infusion of Her2Bi armed ATC and within 1week of the completion of HER2Bi armed ATC) ] [ Designated as safety issue: No ]
|Study Start Date:||October 2001|
|Estimated Study Completion Date:||August 2012|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
- Proleukin ®
- Granulocyte-Macrophage Colony Stimulating Factor
- 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.
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Study Chair:||Lawrence G. Lum, MD, DSc||Barbara Ann Karmanos Cancer Institute|