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

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