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

NCT ID: NCT02173093

Last Updated: 2019-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2019-12-31

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.

Conditions

Disseminated Neuroblastoma; Recurrent Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (IL-2, GM-CSF, GD2Bi-aATC)

Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.

Group Type: EXPERIMENTAL

IL-2

Intervention Type: BIOLOGICAL

Given SC

GD2Bi-aATC

Intervention Type: BIOLOGICAL

Given IV

GM-CSF

Intervention Type: BIOLOGICAL

Given SC

laboratory evaluations of immune responses

Intervention Type: OTHER

Correlative studies

Interventions

IL-2

Given SC

Intervention Type: BIOLOGICAL

GD2Bi-aATC

Given IV

Intervention Type: BIOLOGICAL

GM-CSF

Given SC

Intervention Type: BIOLOGICAL

laboratory evaluations of immune responses

Correlative studies

Intervention Type: OTHER

Other Intervention Names

aldesleukin; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; GD2Bi-armed aATC; sargramostin; Leukine; Prokine; laboratory biomarker analysis

Eligibility Criteria

Inclusion Criteria

• The target tumor is limited to neuroblastoma and the diagnosis should be histologically verified.
• Patients must have refractory or recurrent malignancy; patient's current disease state must be one for which no known curative therapy is available;
• Patients should not receive any other experimental or phase 1 therapy within 3 weeks prior to study enrollment and monoclonal antibody therapy within 6 weeks
• To be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by:

• Local tumor recurrence measurable on CT or magnetic resonance imaging (MRI) scans with or without metastatic lesions
• Refractory bone marrow involvement in patients with NB
• NB with MIBG-positive skeletal lesions
• The presence of radiographically measurable disease immediately prior to start of Phase I immunotherapy is not an eligibility requirement in the following situations:

• In patients with NB who have documented bone marrow (BM) involvement;
• In patients with NB who have MIBG-positive bony lesion(s);
• An additional eligibility requirement for phase II study includes the presence of radiographically measurable disease with the exception of MIBG-positive NB or NB with bone marrow involvement:
• Patients must have a Lansky or Karnofsky performance status score of >= 70
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy

• Myelosuppressive chemotherapy: must not have received within 3 weeks of starting immunotherapy (IT)
• Hematopoietic growth factors: at least 7 days since the last dose of growth factor therapy
• Immunotherapy: at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody
• Normal organ function
• All patients or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

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

• Minimum Eligible Age: 13 Months
• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Daniel W. Lee, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maxim Yankelevich

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status: RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

University of Virginia, Department of Pediatrics, Hematology/Oncology

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Holly Davis

Role: CONTACT

haw5d@virginia.edu

Facility Contacts

Maxim Y. Yankelevich, MD

Role: primary

myankele@med.wayne.edu

313-745-5516

Diana Gomez, MPH

Role: backup

313-745-7163

Shakeel Modak, M.D.

Role: primary

modaks@mskcc.org

Daniel (Trey) Lee, MD

Role: primary

DWL4Q@Virginia.edu

434-297-4289

References

Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.

Reference Type: DERIVED

PMID: 33986124 (View on PubMed)

Other Identifiers

NCI-2014-01149

Identifier Type: REGISTRY

Identifier Source: secondary_id

2013-171

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19031

Identifier Type: -

Identifier Source: org_study_id