PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma

Once a patient has enrolled onto this study, prior therapy will be terminated and patients
will receive temozolomide 200 mg/m2/day x 5 days. If they are receiving bevacizumab at the
time of enrollment, they will continue bevacizumab 10 mg/Kg every 14 days.

Patients who are ≥ 18 years of age will receive a tetanus (Td) booster at the time of
enrollment. Immunotherapy begins with a Tetanus (Td) pre-conditioning vaccine delivered
intrademally (i.d.) in the right groin at the site of the vaccine injection 6-24 hours prior
to the first vaccine on day 21. The first PEP-CMV vaccine will be administered as follows:
Component A mixed with Montanide ISA-51 intradermally administered in the right groin. The
second PEP-CMV vaccine and all subsequent vaccines will be administered as follows: Component
A mixed with Montanide ISA-51 intradermally administered in the right groin and, 2 hours
later, Component B mixed in GM-CSF intradermally administered in the left groin.

The first 3 PEP-CMV vaccines will occur every 2 weeks, then PEP-CMV vaccines will continue
monthly (+/- 2 weeks) until progression. Blood will be obtained for immune monitoring.
Patients will be followed 10 years for tumor progression and/or death due to any cause (if
occurs before end of 10 year follow up).

Inclusion Criteria:

1. Age requirements:

1. 3-17 years old for patients with recurrent WHO grade III/IV glioma

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

2. Histopathologically proven previous diagnosis of medulloblastoma or Grade III or IV
glioma.

3. Radiology evidence of recurrent medulloblastoma (reMB) or recurrent Grade III and IV
glioma. Patients will be considered for a biopsy or resection of the
recurrent/progressive tumor at the discretion of the treating neurosurgeon and
neuro-oncologist.

4. Brain MRI within one month prior to enrollment.

5. Received prior therapy for their initial diagnosis prior to recurrence/progression or
who are unable to receive radiation therapy due to genetic disorders that put them at
significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome
or NF1 mutation).

6. Patients must be CMV seropositive.

7. Patients with neurological deficits should have deficits that are stable for a minimum
of 2 weeks prior to registration.

8. Karnofsky Performance Status (KPS) of ≥ 60% (KPS for > 10 years of age) or Lansky
performance Score (LPS) of ≥ 60 (LPS for ≤ 10 years of age) assessed within 2 weeks
prior to registration. Patients who are unable to walk because of paralysis but who
are up in a wheel chair will be considered ambulatory for the purposes of the
performance score.

9. Bone Marrow:

- ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported)*.

- Platelets ≥ 100,000/µl (unsupported)*.

- Hemoglobin > 8 g/dL (may be supported).

10. Renal:

• Serum creatinine ≤ upper limit of institutional normal.

11. Hepatic:

- Bilirubin ≤ 1.5 times upper limit of normal for age.

- SGPT (ALT) ≤ 3 times institutional upper limit of normal for age.

- SGOT (AST) ≤ 3 times institutional upper limit of normal for age.

12. Patients of childbearing or child-fathering potential must be willing to use a
medically acceptable form of birth control, which includes abstinence, while being
treated on this study.

13. Signed informed consent according to institutional guidelines must be obtained prior
to registration.

14. Any prior chemoradiotherapy is allowed.

Exclusion Criteria:

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

2. Active infection requiring treatment or an unexplained febrile (> 101.5 degrees F)
illness.

3. Known immunosuppressive disease or human immunodeficiency virus infection.

4. Patients with active renal, cardiac (congestive cardiac failure, myocardial
infarction, myocarditis), or pulmonary disease.

5. Patients receiving concomitant immunosuppressive agents for medical condition.

6. Patients who need definitive radiotherapy for treatment of recurrent MB or recurrent
Grade III or IV glioma.

7. Patients receiving any other investigational drug therapy.

8. Patients on corticosteroids > 0.1 mg/Kg/day (i.e. > the maximum dose of 4 mg/day).

9. Patients with any clinically significant unrelated systemic illness (serious
infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).

10. Patients with inability to return for follow-up visits or obtain follow-up studies
required to assess toxicity to therapy.

11. Known allergy or hypersensitivity to Keyhole Limpet Hemocyanin (KLH), Granulocyte
Macrophage Colony Stimulating Factor (GM-CSF) or yeast derived products, or a history
of anaphylactic reactions to shellfish proteins.