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

Phase 1

• Conditions: Recurrent Neuroblastoma; Disseminated Neuroblastoma

• Registration Number: NCT02173093
• Lead Sponsor: University of Virginia

Brief 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.

Study Timeline

• Study First Submitted: 2014-06-22
• Study First Submitted QC: 2014-06-23
• Study First Posted: 2014-06-24
• Study Start: 2014-11
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-25
• Last Update Posted: 2019-01-29
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

• Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are postmenarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 3 months after the last dose of GD2Bi-aATC; breastfeeding women should be excluded
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of GD2Bi-aATC	35 days	Safety of GD2Bi-aATC infusions is evaluated to determine MTD

Secondary Outcome Measures

Name	Time	Method
Anti-tumor activity	Up to 12 months	Objective response rate to GD2Bi-aATC infusions
Immune responses after GD2Bi-aATC infusions	Up to 12 months	In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes

Trial Locations

Locations (3)

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Virginia, Department of Pediatrics, Hematology/Oncology; 🇺🇸 Charlottesville, Virginia, United States