Clinical Trials /

iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma

NCT01953900

Description:

The purpose of this study is to find the largest safe dose of GD2-T cells (also called iC9-GD2-CAR-VZV-CTLs) in combination with a varicella zoster vaccine and lymohodepleting chemotherapy. Additionally, we will learn what the side effects of this treatment are and to see whether this therapy might help patients with advanced osteosarcoma and neuroblastoma. Because there is no standard treatment for recurrent/refractory osteosarcoma and neuroblastoma at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that a new gene can be put into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if a new gene can be put in these cells that will let the T cells recognize and kill sarcoma and neuroblastoma cells. The new gene is called a chimeric antigen receptor (CAR) and consists of an antibody called 14g2a that recognizes GD2, a protein that is found on sarcoma and neuroblastoma cells (GD2-CAR). In addition, it contains parts of the CD28 and OX40 genes which can stimulate T cells to make them live longer. Investigators have found that CAR-T cells can kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. T cells that recognize the virus that causes chicken pox, varicella zoster virus (VZV), remain in the bloodstream for many years especially if they are stimulated or boosted by the VZV vaccine. Investigators will therefore insert the GD2-CAR gene into T cells that recognize VZV. These cells are called iC9-GD2-CAR-VZV-specific T cells but are referred to as GD2-T cells for simplicity.

Related Conditions:
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma/VEGAS

Title

  • Brief Title: iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma/VEGAS
  • Official Title: Vaccination to Enhance the Anti-Tumor Activity of GD2 Chimeric Antigen Receptor-Expressing, VZV-Specific T Cells in Subjects With Advanced Sarcomas (VEGAS)
  • Clinical Trial IDs

    NCT ID: NCT01953900

    ORG ID: H-32335 VEGAS

    NCI ID: VEGAS

    Trial Conditions

    Sarcomas

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    PLEASE NOTE - THIS STUDY IS CURRENTLY ONLY RECRUITING PARTICIPANTS WITH OSTEOSARCOMA.

    The purpose of this study is to find the largest safe dose of GD2-T cells (also called
    iC9-GD2-CAR-VZV-CTLs), and additionally to evaluate if a VZV vaccine can improve the
    expansion and persistence of infused T cells, to learn what the side effects are, and to see
    whether this therapy might help patients with advanced sarcomas. Because there is no
    standard treatment for recurrent/refractory sarcomas at this time or because the currently
    used treatments do not work fully in all cases, patients are being asked to volunteer to
    take part in a gene transfer research study using special immune cells.

    The body has different ways of fighting infection and disease. No single way seems perfect
    for fighting cancers. This research study combines two different ways of fighting cancer:
    antibodies and T cells. Antibodies are types of proteins that protect the body from
    infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special
    infection-fighting blood cells that can kill other cells, including cells infected with
    viruses and tumor cells. Both antibodies and T cells have been used to treat patients with
    cancers. They have shown promise, but have not been strong enough to cure most patients.

    Investigators have found from previous research that a new gene can be put into T cells that
    will make them recognize cancer cells and kill them. Investigators now want to see if a new
    gene can be put in these cells that will let the T cells recognize and kill sarcoma cells.
    The new gene is called a chimeric antigen receptor (CAR) and consists of an antibody called
    14g2a that recognizes GD2, a protein that is found on sarcoma cells (GD2-CAR). In addition,
    it contains parts of the CD28 and OX40 genes which can stimulate T cells to make them live
    longer.

    Investigators have found that CAR-T cells can kill some of the tumor, but they don't last
    very long in the body and so the tumor eventually comes back. T cells that recognize the
    virus that causes chicken pox, varicella zoster virus (VZV), remain in the bloodstream for
    many years especially if they are stimulated or boosted by the VZV vaccine. Investigators
    will therefore insert the GD2-CAR gene into T cells that recognize VZV. These cells are
    called iC9-GD2-CAR-VZV-specific T cells but are referred to as GD2-T cells for simplicity.

    Detailed Description

    Patients give blood to make GD2-T cells that are grown and frozen. To get the GD2-CAR to
    attach to the surface of the T-cell, a gene is inserted into the T-cell. As described in the
    Brief Summary, the gene contains the GD2-CAR. This is done using part of a virus (known as a
    retrovirus) that has been put into a vector made for this study and that will carry the
    antibody gene into the T cell. This retrovirus vector also helps identify the T cells in the
    patient's blood after they have been injected. Because the patients have received cells with
    a new gene in them they will be followed for a total of 15 years to see if there are any
    long term side effects of gene transfer.

    When enrolled on this study, patients will be assigned to one of two groups of different
    doses of GD2-T cells. The first group of patients will receive a lower dose of GD2-T cells.
    Once that dose schedule proves safe, the next group of patients will be started at the
    higher dose. Before receiving the dose of GD2-T cells, they will receive a dose of the VZV
    vaccine.

    This will be given as an injection under the skin and will take less than a minute. Two days
    later patient will be given an injection of GD2-T cells into the vein through an IV line at
    the assigned dose. Before the injection is received, a dose of Benadryl and Tylenol may be
    given. The injection will take between 1 and 25 minutes. After the injection the patient
    will be followed in the clinic for up to 4 hours. The treatment will be given by the Center
    for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. The
    patient may need to stay in Houston for up to 4 weeks after the infusion to monitotor for
    side effects.

    We will follow the patient in the clinic or through communication with their primary doctor
    after the GD2-T-cell injection.

    Medical tests before treatment--

    Before being treated, patients will receive a series of standard medical tests:

    - Physical exam

    - Blood tests to measure blood cells, kidney and liver function

    - Measurements of their tumor by routine imaging studies. We will use the imaging study
    that was used before to follow the patient's tumor (Computer Tomogram (CT), Magnetic
    Resonance Imaging (MRI), or Positron Emission Tomography(PET/CT)

    Medical tests during and after treatment--

    Patients will receive standard medical tests when they are getting the infusions and
    afterwards:

    - Physical exams

    - Blood tests to measure blood cells, kidney and liver function

    - Measurements of their tumor by routine imaging studies at 6 weeks after the infusion

    To learn more about the way the GD2-T cells are working and how long they last in the body,
    an extra amount of blood, based on the patient's weight, up to a maximum of 60 ml (12
    teaspoons) of blood will be taken on the day of the GD2-T- cell infusion(s), (before and at
    the end of the T-cell infusion(s)), 1, 2, 4, and 6 weeks after the GD2-T-cell infusion(s)
    and every 3 months for 1 year, at 15 months and 18 months, then every 6 months for 4 years,
    then yearly for a total of 15 years. One additional blood sample might be drawn 3 to 4 days
    after the GD2-T-cell infusion(s); this is optional. Blood may be drawn at additional time
    points based on the patient's response to the treatment.

    During the time points listed above, if the Tcells are found in patient's blood at a certain
    amount, an extra 5ml of blood may need to be collected for additional testing.

    For children, the total amount of blood drawn will not be more than 3 ml (less than 1
    teaspoon) per 2.2 lbs of body weight on any one day. This volume is considered safe, but may
    be decreased if the patient is anemic (have a low red blood cell count).

    Trial Arms

    Name Type Description Interventions
    GD2 T cells plus VZV vaccine Experimental

    Eligibility Criteria

    Inclusion Criteria:

    Procurement:

    - Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard
    treatment. Patients with osteosarcoma do not require GD2 testing of their tumor as
    osteosarcomas are uniformly GD2 positive.

    - Either previously infected with varicella zoster virus(VZV; chicken pox) or
    previously vaccinated with VZV vaccine

    - Karnofsky/Lansky score of greater than or equal to 50

    - Informed consent explained to, understood by and signed by patient/guardian.
    Patient/guardian given copy of informed consent

    Treatment:

    - Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard
    treatment. Patients with osteosarcoma do not require GD2 testing of their tumors as
    osteosarcomas are uniformly GD2 positive.

    - Recovered from the acute toxic effects of all prior chemotherapy

    - Karnofsky/Lansky score of greater than or equal to 50

    - Bilirubin less than or equal to 3x upper limit of normal, AST less than or equal to
    5x upper limit of normal, Serum creatinine less than or equal to 2x upper limit of
    normal, Hgb greater than or equal to 9.0 g/dl, ANC>500/uL, platelets > 50,000/uL

    - Pulse oximetry of greater than or equal to 90% on room air

    - Sexually active patients must be willing to utilize one of the more effective birth
    control methods for 6 months after the CTL infusion. Male partner should use a
    condom.

    - Available autologous transduced cytotoxic T lymphocytes with greater than or equal to
    20% expression of GD2 CAR and killing of GD2-positive targets greater than or equal
    to 20% in cytotoxicity assay

    - Informed consent explained to, understood by and signed by patient/guardian.
    Patient/guardian given copy of informed consent

    Exclusion Criteria:

    Procurement:

    Known primary immune deficiency or HIV positivity

    Treatment:

    - Severe intercurrent infection

    - Known primary immune deficiency or HIV positivity

    - Pregnant or lactating

    - History of hypersensitivity reactions to murine protein-containing products

    - Known allergy to VZV vaccine

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of subjects with a dose limiting toxicity

    Secondary Outcome Measures

    Number of patients with a response to the T cells

    Amount of T cells in the blood after the infusions

    Trial Keywords

    Sarcoma

    T-Cells

    varicella zoster virus (VZV)

    GD2