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



Status:Recruiting
Conditions:Cancer, Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:3/8/2019
Start Date:April 2014
End Date:April 2036
Contact:Sarah Whittle, MD
Email:sbwhittl@txch.org
Phone:832-824-1471

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Vaccination to Enhance the Anti-Tumor Activity of GD2 Chimeric Antigen Receptor-Expressing, VZV-Specific T Cells in Subjects With Advanced Sarcomas and Neuroblastoma (VEGAS)

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.

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 three 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. Patients will receive treatment with with cyclophosphamide (cytoxan) and fludarabine
for 3 days before receiving the T-cell infusion. These drugs will decrease the numbers of
your own T cells before we infuse the GD2-T cells.

Patients will receive the GD2-T cells by an intravenous line. Before patients receive the
injection, they may be given a dose of Benadryl and Tylenol. The injection will take between
1 and 25 minutes. The research team will follow patients in the clinic after the injection
for 1 to 4 hours. Two weeks after receiving the dose of GD2-T cells, patients will receive a
dose of the VZV vaccine. This will be given as an injection under the skin that will take
less than a minute. The treatment will be given by the Center for Cell and Gene Therapy at
Texas Children's Hospital or Houston Methodist Hospital. Patients may need to stay in Houston
for up to 4 weeks after the infusion so the research team can monitor patients for side
effects. The research team will follow patients 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 and History

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

- A urine pregnancy test. If you a patient is pregnant, both the patient and her parents
will be informed of the pregnancy

- 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 pounds 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).

Inclusion Criteria:

Procurement:

- Diagnosis of relapsed or refractory osteosarcoma OR relapsed or refractory high risk
neuroblastoma not responsive to standard treatment.

- 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 relapsed or refractory osteosarcoma OR relapsed or refractory high risk
neuroblastoma not responsive to standard treatment.

- 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 7.0 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
We found this trial at
2
sites
6550 Fannin St
Houston, Texas 77030
(713) 790-3311
Principal Investigator: Lisa L Wang, MD
Phone: 832-824-4822
Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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6621 Fannin St
Houston, Texas 77030
(832) 824-1000
Principal Investigator: Sara Whittle, MD
Phone: 832-824-1471
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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Houston, TX
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