Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

It is believed that the body's immune system protects the body by attacking and killing tumor
cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they
recognize special proteins on the surface of tumors. But in most patients with advanced
cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will
use your tumor to make a vaccine which we hope will stimulate your T-cells to kill tumor
cells and leave your normal cells alone.

High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to
attack. Before T-cells can become active against tumor cells, they require strong stimulation
by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of
the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes,
and create this strong stimulation.

The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC
vaccines can be given safely. Most importantly, this study is also to determine whether the
T-cells and DC vaccines can stimulate your immune system to fight off the tumor cells in your
brain. When the vaccine for this study is made, dendritic cells will be loaded with genetic
material called RNA (ribonucleic acid) from your tumor to stimulate the dendritic cells. The
vaccine has two components given at different times after chemoradiation and throughout
chemotherapy cycles. The first part, the DC vaccine, involves RNA loaded dendritic cells that
are given under the skin at several time points in the study and the second part, xALT
vaccine, is a single infusion of tumor-specific T cells delivered through one of two
peripheral IV catheters that are placed prior to infusion. This vaccine is investigational
which means that it is not approved by the US Food and Drug Administration (FDA) and is being
tested in research studies.

It is hoped that by injecting the DC vaccine into your skin and infusing the T-cells into
your blood, your immune system will be activated against the tumor. Once it is activated
against the tumor, your immune system may recognize and attack the tumor cells in your brain
and not attack normal cells. Use of a vaccine that stimulates your immune system is called
immunotherapy.

Screening Eligibility:

- Patients with histologically confirmed WHO Grade III or IV malignant glioma

- Scheduled for definitive surgical resection of suspected HGG (biopsy only subjects are
not eligible for this study)

Post-Surgical Resection Eligibility

- Histologically confirmed WHO Grade III or IV malignant glioma

- Residual post-surgical disease burden < 3 cm as defined by longest perpendicular
diameter of contrast enhancing tumor on post-operative MRI Karnofsky Performance
Status (KPS) of > 60% (KPS for > 16 years of age) or Lansky performance Score (LPS) of
≥ 60 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration

- Bone Marrow: ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported); Platelets ≥
100,000/µl (unsupported for at least 3 days); Hemoglobin > 8 g/dL (may be supported)

- Renal:Serum creatinine ≤ upper limit of institutional normal Hepatic: Bilirubin ≤ 1.5
times upper limit of institutional normal for age. SGPT (ALT) ≤ 3 times upper limit of
institutional normal for age. SGOT (AST) ≤ 3 times upper limit of institutional normal
for age.

- Signed informed consent according to institutional guidelines.

- Patient or patient guardian consent to PBSC harvest following registration.

- Subjects of childbearing or child-fathering potential must be willing to use medically
acceptable forms of birth control while being treated on this study.

- Subjects with post-surgical neurological deficits should have deficits that are stable
for a minimum of 1 week prior to registration.

Prior to 1st Vaccine

- Off corticosteroids or weaning to a minimal/stable dose of replacement steroids ≤ 4
mg/day within 1 week of scheduled DC vaccination.

Exclusion Criteria:

- HGG biopsy only subjects are not eligible for this study

- Midline unresectable tumors

- Gliomatosis Cerebri

- Residual post-surgical disease burden > 3 cm as defined by longest perpendicular
diameter of contrast enhancing tumor on MRI.

- Pregnant or need to breast feed during the study period (Negative serum pregnancy test
required).

- Known autoimmune or immunosuppressive disease or human immunodeficiency virus
infection.

- Subjects with significant renal, cardiac (congestive cardiac failure, myocardial
infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.

- Subjects who require corticosteroids above physiologic doses (>4mg/day or equivalent
dexamethasone).

- Severe or unstable concurrent medical conditions.

- Prior allergic reaction to TMZ, GM-CSF, or Td

- Subjects who are unwilling or unable to receive treatment and undergo follow-up
evaluations at the enrolled Sunshine Project Consortium treatment site.