Cytomegalovirus (CMV) RNA-Pulsed Dendritic Cells for Pediatric Patients With Newly Diagnosed WHO Grade IV Glioma, Recurrent Malignant Glioma, or Recurrent Medulloblastoma

Participants in this study will undergo a leukapheresis procedure in which blood is collected
into a machine that removes white blood cells and then returns the remainder of the blood
back to the individual. The white blood cells removed from the blood are used to make the
participant's study vaccine. Newly diagnosed patients will undergo standard radiation therapy
(RT) with or without temozolomide after leukapheresis. If a patient is experiencing a
recurrence, the study doctor may recommend "bridge therapy" after leukapheresis. Bridge
therapy is approved or standard therapy for the tumor intended to bridge the time without the
study drugs, dose-intensified temozolomide (DI-TMZ) or CMV-DC vaccine. All participants will
undergo a cycle of "dose-intensified" temozolomide (DI-TMZ will start about 4 weeks after
completing standard RT for newly diagnosed patients and about 3 weeks after leukapheresis for
recurrent patients). Participants will receive Td pre-conditioning given as a shot in the
right leg, six to 24 hours before receiving their 1st vaccine, which is also given as shots
in the legs. Vaccines #2 and #3 will occur at 2-week intervals after the 1st vaccine. After
the 3rd vaccine, there will be 4 weeks between vaccines for as many vaccines as the study
team can prepare from the participant's leukapheresis.

Inclusion Criteria:

1. Age requirements:

1. ≤ 18 years for patients with recurrent World Health Organization (WHO) grade III
or IV glioma

2. 3-35 years old for patients with recurrent medulloblastoma

2. Newly diagnosed or recurrent WHO grade IV glioma, recurrent WHO grade III glioma, or
recurrent medulloblastoma (multifocal/disseminated disease is eligible, at the
discretion of the PI)

3. Patients must have recovered from all previous treatments including chemotherapy,
radiation therapy, surgery, and other immunotherapies, etc.

4. Laboratory Studies:

1. Platelets ≥ 100,000 cells/mm3

2. Creatinine ≤ 1.2 x upper limit of normal (ULN)

3. Total bilirubin, Aspartate Aminotransferase (AST), Alanine Aminotransferase
(ALT), alkaline phosphatase ≤ 2.5 x ULN

4. Neutrophil count ≥ 1000 cells/mm3

5. Hemoglobin ≥ 9 g/dl prior to biopsy (can be transfused)

5. Able to undergo brain MRI with and without contrast

6. Karnofsky Performance Status (KPS) ≥ 70 or Lansky Performance Status (LPS) ≥ 70

7. A signed informed consent form approved by the Institutional Review Board (IRB) will
be required for patient enrollment into the study. Patients (if 18 years old or older)
or their parent(s) or guardian(s) (if younger than 18 years old) must be able to read
and understand the informed consent document and must sign the informed consent
indicating that they are aware of the investigational nature of this study.

8. For females of childbearing potential, negative serum pregnancy test within 48 hours
of leukapheresis

9. Females of childbearing potential must be willing to use acceptable contraceptive
method to avoid pregnancy throughout the study and for at least 24 weeks after the
last dose of study drug

10. Males with female partners of childbearing potential must agree to practice adequate
contraceptive methods throughout the study and should avoid conceiving children for 24
weeks following the last dose of study drug

11. Newly diagnosed WHO grade IV glioma patients only: must be expected to complete
standard of care radiation (minimum ~54 Gray)

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease
free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and
cervix are all permissible)

2. Disease outside of the central nervous system (CNS)

3. Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C seropositive

4. Known active infection requiring intravenous (IV) antibiotics or active
immunosuppressive disease

5. Severe, active co-morbidity, defined as follows:

1. Unstable angina and/or congestive heart failure requiring hospitalization

2. Transmural myocardial infarction within the last 6 months

3. Acute bacterial or fungal infection requiring intravenous antibiotics at
initiation of Radiation Therapy (XRT)/Temozolomide (TMZ)

4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at initiation of XRT/TMZ
for newly diagnosed patients or at initiation of dose-intensified (DI) TMZ for
recurrent patients

5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

6. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition. The need to exclude patients with AIDS
from this protocol is necessary because the treatments involved in this protocol
may be significantly immunosuppressive

7. Patients with autoimmune disease requiring medical management with
immunosuppressant(s)

8. Major medical illnesses or psychiatric impairments that, in the investigator's
opinion, will prevent administration or completion of protocol therapy

9. Active connective tissue disorders such as lupus or scleroderma that, in the
investigator's opinion, place the patient at high risk for radiation toxicity

6. Pregnant or lactating women

7. Prior allergy to TMZ, GM-CSF, gadolinium (Gd), or Td

8. Prior history of brachial neuritis or Guillain-Barré syndrome

9. Patients treated on any other therapeutic clinical protocols within 30 days prior to
study entry

10. For recurrent patients only: Patients who have not recovered from the toxic effects of
prior chemo- and/or radiation therapy. Guidelines for this recovery period are
dependent upon the specific therapeutic agent being used:

1. Patients who have received chemotherapy or bevacizumab ≤ 4 weeks [except for
nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or
cyclophosphamide (1 week)] prior to starting the study drug unless patients have
recovered from the side effects of such therapy

2. Patients who have received immunotherapy ≤ 4 weeks prior to starting the study
drug unless patients have recovered from the side effects of such therapy