NCT02173093

Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma

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

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: All
• Age: 13 Months – 29 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Disseminated Neuroblastoma
• Recurrent Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	IL-2	Given SC
BIOLOGICAL	GD2Bi-aATC	Given IV
BIOLOGICAL	GM-CSF	Given SC
OTHER	laboratory evaluations of immune responses	Correlative studies

Timeline

• Start date: 2014-11-01
• Primary completion: 2019-12-01
• Completion: 2019-12-01
• First posted: 2014-06-24
• Last updated: 2019-01-29

Locations

3 sites across 1 country: United States