We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02173093
Recruitment Status : Unknown
Verified January 2019 by Daniel W. Lee, MD, University of Virginia.
Recruitment status was:  Recruiting
First Posted : June 24, 2014
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Daniel W. Lee, MD, University of Virginia

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Disseminated Neuroblastoma Recurrent Neuroblastoma Biological: IL-2 Biological: GD2Bi-aATC Biological: GM-CSF Other: laboratory evaluations of immune responses Phase 1 Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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:
  • aldesleukin
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2

Biological: GD2Bi-aATC
Given IV
Other Name: GD2Bi-armed aATC

Biological: GM-CSF
Given SC
Other Names:
  • sargramostin
  • Leukine
  • Prokine

Other: laboratory evaluations of immune responses
Correlative studies
Other Name: laboratory biomarker analysis


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of GD2Bi-aATC [ Time Frame: 35 days ]
    Safety of GD2Bi-aATC infusions is evaluated to determine MTD


Secondary Outcome Measures :
  1. Anti-tumor activity [ Time Frame: Up to 12 months ]
    Objective response rate to GD2Bi-aATC infusions

  2. 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   13 Months to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

The study is now in the phase II expansion phase.

Inclusion Criteria for phase II:

  • 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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Holly Davis haw5d@virginia.edu

Locations
Layout table for location information
United States, Michigan
Children's Hospital of Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Maxim Y. Yankelevich, MD    313-745-5516    myankele@med.wayne.edu   
Contact: Diana Gomez, MPH    313-745-7163      
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.       modaks@mskcc.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         
Sponsors and Collaborators
University of Virginia
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Maxim Yankelevich Barbara Ann Karmanos Cancer Institute
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Daniel W. Lee, MD, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier: NCT02173093    
Other Study ID Numbers: 19031
NCI-2014-01149 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2013-171 ( Other Identifier: Barbara Ann Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
First Posted: June 24, 2014    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
Keywords provided by Daniel W. Lee, MD, University of Virginia:
Neuroblastoma
Solid tumor
Immunotherapy targeting GD2
Bispecific antibodies
Activated T cells
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aldesleukin
 Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents