Inclusion Criteria:

- Histologically confirmed* primary CNS high-grade glioma, including any of the
following:

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma,
anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)

- No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord
high-grade astrocytoma

- Gliosarcoma

- Recurrent or progressive disease that is refractory to standard therapy

- Radiographically documented measurable disease

- Lesion must be at least twice the thickness of the image from which it is
derived (e.g., 10 mm for a 5 mm slice thickness)

- No diffuse pontine gliomas

- No evidence of prior CNS bleeding

- Karnofsky performance status (PS) 50-100% (patients > 16 years of age)

- Lansky PS 50-100% (patients ≤ 16 years of age)

- Life expectancy ≥ 8 weeks

- ANC ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70mL/min OR serum
creatinine based on age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4mg/dL (female) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT and AST ≤ 2.5 times ULN for age

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94%, if determination is clinically indicated

- Seizure disorder is allowed provided it is well-controlled with anticonvulsants

- No uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Recovered from all prior therapy

- No more than two prior treatments for high-grade glioma (i.e., one initial treatment
and one treatment for relapse)

- More than 2 weeks since prior myelosuppressive chemotherapy (≥ 6 weeks for
nitrosoureas)

- At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or
biologic therapy

- At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a
symptomatic non-target lesion only

- At least 3 months since prior craniospinal radiotherapy

- At least 6 weeks since prior substantial bone marrow radiotherapy

- At least 6 months since prior allogeneic stem cell transplantation (SCT) or rescue

- Patients who have undergone prior allogeneic SCT and who have graft-versus-host
disease (GVHD) must have controlled GVHD that is ≤ grade 2

- At least 1 month since prior autologous SCT

- More than 1 week since prior growth factors (> 3 weeks for pegfilgrastim [Neulasta®])

- No other concurrent anticancer therapy, including chemotherapy or immunomodulating
agents

- No other concurrent experimental agents or therapies

- No concurrent alternative or complimentary therapies

- No concurrent homeopathic medicines

- No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid
(aspirin)

- No concurrent steroids as anti-emetics

- Concurrent steroids for treatment of increased intracranial pressure allowed if on a
stable or decreasing dose for ≥ 1 week before study entry

- Concurrent radiotherapy to localized painful lesions allowed provided ≥ 1 measurable
lesion is not irradiated