Recurrent Neuroblastoma Clinical Trial
Official title:
Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study
Previous research has demonstrated that investigators can coat (arm) T cells with a special molecule called GD2 bispecific antibody that will help T cells recognize neuroblastoma and osteosarcoma cells and kill them. This bispecific antibody recognizes GD2, a protein found on almost all neuroblastoma and osteosarcoma cells. The investigators put the GD2 bispecific antibody on T cells and give large numbers of these T cells back to patients. The investigators think that these T cells may have a better chance of killing GD2 expressing tumor cells when they are armed with GD2 bispecific antibody. This trial studies the side effects and best dose of activated T cells armed with GD2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other GD2-positive solid tumors.
PRIMARY OBJECTIVES:
I. To perform a phase I dose-escalation study in patients with recurrent or refractory
neuroblastoma (NB) and other GD2-positive tumors to evaluate the safety and tolerability and
to determine the maximum tolerated dose (MTD) for anti-CD3 x hu3F8 bispecific antibody
(GD2Bi)-armed activated T cells (aATC) infused twice a week for a total of eight infusions in
combination with daily IL-2 (300,000 IU/m^2/day) and GM-CSF (250 ug/m^2 twice per week) in a
standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10^6 cells/kg/infusion dose
levels.
II. To conduct a phase II clinical trial to explore efficacy and confirm the toxicity profile
of GD2Bi-aATC combined with IL-2 and GM-CSF in a phase II expansion cohort of 22 patients
with neuroblastoma (NB) using MTD determined in the phase I.
SECONDARY OBJECTIVES:
I. Evaluate immune responses in the phase I/II trial by sequential monitoring of anti-NB
cytotoxicity of peripheral blood lymphocytes and IFN-gamma EliSpots directed at NB lines.
II. To evaluate persistence of aATC in the blood and tumor biopsies by staining for murine
IgG2a to confirm trafficking of armed T cells to tumor.
III. To conduct exploratory study of (18F FDG) positron emission tomography (PET)/computed
tomography (CT) after armed ATC infusions in selected patients with PET/CT measurable soft
tissue and skeletal lesions.
OUTLINE: This is a phase I, dose-escalation study of OKT3/humanized 3F8 bispecific
antibody-aATC followed by a phase II study.
Patients receive IL-2 subcutaneously (SC) daily on days -2 to 35, sargramostim SC twice
weekly for 4 weeks, and OKT3/humanized 3F8 bispecific antibody-aATC intravenously (IV) over
30 minutes twice weekly for 4 weeks.
After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.
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