Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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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/m2/day) and GM-CSF (250 ug/m2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10^6 cells/kg/infusion dose levels.
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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:
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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.
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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.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: IL-2
Given SC
Other Names:
Biological: GD2Bi-aATC
Given IV
Other Names:
Biological: GM-CSF
Given SC
Other Names:
Other: laboratory evaluations of immune responses
Correlative studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) of GD2Bi-aATC [35 days]
Safety of GD2Bi-aATC infusions is evaluated to determine MTD
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
The study is now in the phase II expansion phase.
Inclusion Criteria for phase II:
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The target tumor is limited to neuroblastoma and the diagnosis should be histologically verified.
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Patients must have refractory or recurrent malignancy; patient's current disease state must be one for which no known curative therapy is available;
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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
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To be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by:
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Local tumor recurrence measurable on CT or magnetic resonance imaging (MRI) scans with or without metastatic lesions
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Refractory bone marrow involvement in patients with NB
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NB with MIBG-positive skeletal lesions
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The presence of radiographically measurable disease immediately prior to start of
Phase I immunotherapy is not an eligibility requirement in the following situations:
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In patients with NB who have documented bone marrow (BM) involvement;
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In patients with NB who have MIBG-positive bony lesion(s);
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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:
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Patients must have a Lansky or Karnofsky performance status score of >= 70
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Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
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Myelosuppressive chemotherapy: must not have received within 3 weeks of starting immunotherapy (IT)
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Hematopoietic growth factors: at least 7 days since the last dose of growth factor therapy
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Immunotherapy: at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody
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Normal organ function
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All patients or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
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All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
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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
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Patients who have an uncontrolled infection are not eligible
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Michigan | Detroit | Michigan | United States | 48201 |
| 2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 3 | University of Virginia, Department of Pediatrics, Hematology/Oncology | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- University of Virginia
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Maxim Yankelevich, Barbara Ann Karmanos Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19031
- NCI-2014-01149
- 2013-171
- P30CA022453