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

January 25, 2019 updated by: Daniel W. Lee, MD, University of Virginia

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Children's Hospital of Michigan
        • Contact:
        • Contact:
          • Diana Gomez, MPH
          • Phone Number: 313-745-7163
        • Principal Investigator:
          • Maxim Y. Yankelevich, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
        • Contact:
        • Principal Investigator:
          • Shakeel Modak, M.D.
        • Sub-Investigator:
          • Alexandar Chou, M.D.
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia, Department of Pediatrics, Hematology/Oncology
        • Contact:
        • Principal Investigator:
          • Daniel (Trey) Lee, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 29 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
  • aldesleukin
Biological: GD2Bi-aATC
Given IV
Other Names:
  • GD2Bi-armed aATC
Biological: GM-CSF
Given SC
Other Names:
  • Leukine
  • Prokine
  • sargramostin
Other: laboratory evaluations of immune responses
Correlative studies
Other Names:
  • laboratory biomarker analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) of GD2Bi-aATC
Time Frame: 35 days
Safety of GD2Bi-aATC infusions is evaluated to determine MTD
35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-tumor activity
Time Frame: Up to 12 months
Objective response rate to GD2Bi-aATC infusions
Up to 12 months
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
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Maxim Yankelevich, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

June 22, 2014

First Submitted That Met QC Criteria

June 23, 2014

First Posted (Estimate)

June 24, 2014

Study Record Updates

Last Update Posted (Actual)

January 29, 2019

Last Update Submitted That Met QC Criteria

January 25, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19031
  • P30CA022453 (U.S. NIH Grant/Contract)
  • 2013-171 (Other Identifier: Barbara Ann Karmanos Cancer Institute)
  • NCI-2014-01149 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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