Phase II Pegylated Interferon

Low grade gliomas are the most common pediatric central nervous system malignancies and can
occur in different parts of the brain. Patients who undergo gross total resection, usually
those with hemispheric tumors, have an excellent prognosis with surgical resection alone.
Patients for whom gross total resection is not achievable have a significant risk of disease
progression. Therefore, these patients benefit from adjuvant therapy. Multiple chemotherapy
regimens have shown some efficacy in residual tumor, but more than 50% of patients experience
recurrences. Radiation has been shown to be an effective therapy in the treatment of these
tumors. Because of concerns regarding radiation toxicity especially in young children, and
progression despite chemotherapy, novel approaches are needed. This protocol represents an
attempt to measure the efficacy and safety of use of pegylated interferon for patients with
recurrent, refractory Juvenile Pilocytic Astrocytomas (JPA) or optic pathway gliomas. It
provides a different approach to the commonly used treatment modalities. The objectives of
this study are to determine the response of children with chemotherapy-refractory progressive
JPA or optic pathway gliomas (OPG) to weekly pegylated interferon alpha-2b. The secondary
objectives include to better identify the toxicities of weekly pegylated interferon alpha-2b
(PEG-Intron™) in pediatric patients with unresectable, refractory, recurrent JPAs or optic
pathway gliomas, to evaluate various magnetic resonance imaging techniques for noninvasive
monitoring of metabolic and biologic changes in the tumors and to evaluate the quality of
life for patients with recurrent, refractory JPAs who receive therapy with pegylated
interferon alpha-2b (PEG-Intron™).

The primary end point is to determine the response rate. A two-stage design has been selected
to evaluate the response rate. If the treatment demonstrates at least a 25% response rate,
the researchers would consider it a promising regimen for further study. A response rate less
than 5% is considered evidence of unpromising regimen. Seventeen evaluable pediatric patients
with JPA or OPG will be accrued. If at least 3 responders are seen among the 17 patients,
this will be considered evidence of a promising response rate for further evaluation.

Inclusion Criteria:

- Patients must be older than 3 years and less than 18 years of age at the time of
enrollment

- Patients with neurofibromatosis are eligible

- Histologic confirmation is not required for this if the patient has NF-1 with MRI
findings consistent with optic pathway glioma or JPA. Any other tumors will need
histological confirmation, either at the time of diagnosis or at the time of
recurrence. The histological diagnosis includes WHO grade I JPA

- Patients must have measurable residual disease, defined as tumor that is measurable in
two or three perpendicular diameters on MRI. For a lesion to be considered measurable,
it must be at least twice the slice thickness on MRI (i.e visible on more than one
slice)

- All patients must have a brain MRI with and without contrast (gadolinium) within 30
days prior to study enrollment. All patients with history of spinal or leptomeningeal
disease and those patients with symptoms suspicious of spinal disease, must have a
spine MRI with contrast ( gadollinium) performed within 30 days prior to study
enrollment. Lumbar Puncture is necessary if there is evidence of tumor dissemination
on the MRI of spine

- Performance Level: Karnofsky >or equal to 50% for patients > 10 years of age or Lansky
> or equal to 50 for patients < 10 years of age

- Patients must have recovered (to CTC v.4.0 ≤ Grade 1 unless indicated below) from the
acute toxic effects of all prior chemotherapy, immunotherapy prior to entering this
study, with the exception of alopecia, weight changes and Grade I or II lymphopenia

- At least 7 days must have elapsed since the completion of therapy with other biologic
agents. For other biologic agents that have known adverse events occurring beyond 7
days after administration, this period must be extended beyond the time during which
adverse events are known to occur

- At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
Specifically for bevacizumab 36 days after the last dose

- At least 3 weeks from the last surgical resection, prior to start study drug

- At least 42 days after the completion of any type of immunotherapy, e.g. tumor
vaccines

- Patients must have had their last fraction of cranial or craniospinal Radiation ≥ 24
months prior to study entry

- Adequate organ function

Exclusion Criteria:

- Patients who are receiving concurrent chemotherapy, or who are currently receiving
other investigational chemotherapeutic agents or concurrently receiving radiation

- Patients with a known hypersensitivity to interferon-alpha

- Prior use of Peg-intron or interferon

- Less than 2 years since completion of radiation therapy

- Pregnant or breast-feeding females are excluded

- Patients with clinically significant unrelated systemic illness

- Dental braces or prosthesis that interferes with MR imaging

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol

- Patients with a positive history of Hepatitis B or Hepatitis C

- Patient with diagnosis of Diffuse Intrinsic Pontine Glioma