Clinical Trials /

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

NCT02173093

Description:

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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 19031
  • SECONDARY ID: NCI-2014-01149
  • SECONDARY ID: 2013-171
  • SECONDARY ID: P30CA022453
  • NCT ID: NCT02173093

Conditions

  • Disseminated Neuroblastoma
  • Recurrent Neuroblastoma

Interventions

DrugSynonymsArms
IL-2aldesleukin, Proleukin, recombinant human interleukin-2, recombinant interleukin-2Treatment (IL-2, GM-CSF, GD2Bi-aATC)
GD2Bi-aATCGD2Bi-armed aATCTreatment (IL-2, GM-CSF, GD2Bi-aATC)
GM-CSFsargramostin, Leukine, ProkineTreatment (IL-2, GM-CSF, GD2Bi-aATC)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (IL-2, GM-CSF, GD2Bi-aATC)ExperimentalPatients 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.
  • IL-2
  • GD2Bi-aATC
  • GM-CSF

Eligibility 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
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:13 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Anti-tumor activity
Time Frame:Up to 12 months
Safety Issue:
Description:Objective response rate to GD2Bi-aATC infusions
Measure:Immune responses after GD2Bi-aATC infusions
Time Frame:Up to 12 months
Safety Issue:
Description:In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Virginia

Trial Keywords

  • Neuroblastoma
  • Solid tumor
  • Immunotherapy targeting GD2
  • Bispecific antibodies
  • Activated T cells

Last Updated

January 25, 2019