Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
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|ClinicalTrials.gov Identifier: NCT02173093|
Recruitment Status : Recruiting
First Posted : June 24, 2014
Last Update Posted : December 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Desmoplastic Small Round Cell Tumor Disseminated Neuroblastoma Metastatic Osteosarcoma Recurrent Neuroblastoma Recurrent Osteosarcoma||Biological: IL-2 Biological: GD2Bi-aATC Biological: GM-CSF Other: laboratory evaluations of immune responses||Phase 1 Phase 2|
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||November 2014|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||May 2018|
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.
Other Name: GD2Bi-armed aATC
Other: laboratory evaluations of immune responses
Other Name: laboratory biomarker analysis
- Maximum tolerated dose (MTD) of GD2Bi-aATC [ Time Frame: 35 days ]Safety of GD2Bi-aATC infusions is evaluated to determine MTD
- Anti-tumor activity [ Time Frame: Up to 12 months ]Objective response rate to GD2Bi-aATC infusions
- Immune responses after GD2Bi-aATC infusions [ Time Frame: Up to 12 months ]In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02173093
|United States, Michigan|
|Children's Hospital of Michigan||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Maxim Y. Yankelevich, MD 313-745-5516 email@example.com|
|Contact: Kathy Miller, RN 313-745-8214|
|Principal Investigator: Maxim Y. Yankelevich, MD|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Shakeel Modak, M.D. firstname.lastname@example.org|
|Principal Investigator: Shakeel Modak, M.D.|
|Sub-Investigator: Alexandar Chou, M.D.|
|United States, Virginia|
|University of Virginia, Department of Pediatrics, Hematology/Oncology||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Daniel (Trey) Lee, MD 434-297-4289 DWL4Q@Virginia.edu|
|Principal Investigator: Daniel (Trey) Lee, MD|
|Principal Investigator:||Maxim Yankelevich||Barbara Ann Karmanos Cancer Institute|