Immunologic Effects of GM-CSF (Sargramostim, Leukine®) in Patients With Biochemically-relapsed Prostate Cancer
- To determine the ability of sargramostim (GM-CSF) to increase the number and activation
of dendritic cells (DC) in patients with biochemically relapsed prostate cancer.
- To determine the effect of administration schedule and hormonal state on
sargramostim-induced DC number and activation in these patients.
- To correlate the effects of sargramostim on DC number and activation with effects on
prostate-specific antigen (PSA) modulation.
- To determine whether sargramostim administration generates antiprostate cancer immune
responses in these patients.
OUTLINE: Patients are stratified according to hormonal status (androgen-dependent vs
androgen-independent). Patients are then randomized to 1 of 2 treatment arms.
- Arm I: Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14.
Treatment repeats every 28 days for 6 courses in the absence of disease progression or
- Arm II: Patients receive GM-CSF SC three times weekly for 4 weeks. Treatment repeats
every 28 days for 6 courses in the absence of disease progression or unacceptable
Patients undergo blood sample collection periodically for correlative studies. Samples are
analyzed for dendritic cell (DC) number by flow cytometry, DC activation by quantitative
real-time polymerase chain reaction (QRT-PCR), and immunity by serological analysis of
recombinant cDNA expression libraries (SEREX).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dendritic cell (DC) activation index post-sargramostim vs pre-sargramostim
DC (lin- CD4+) will be purified from peripheral blood using a magnetic cell sorting kit. The number of DC isolated will be expressed per ml of blood. (This will provide an independent method of quantifying total DC population). Activation of the cells separated will be evaluated by assessing the ratio of IL-12(p40) to IL-10 mRNA as quantified by QRT-PCR. A DC activation index will be calculated for each sample by multiplying the number of DC per ml of blood by the ratio of IL-12/IL-10 mRNA expressed.
pre-tx and q 2 weeks during tx and post tx
Robert Dreicer, MD, FACP
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
United States: Institutional Review Board
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|