• INCLUSION CRITERIA:

Age: Greater than or equal to 18 months to 21 years of age

Diagnosis: Patients with NF1 and an inoperable plexiform neurofibroma that has the potential to cause significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings. However, if any clinical observation or scan suggests possible malignant transformation, the tumor should be biopsied prior to therapy. Patients without biopsy-proof of a plexiform neurofibroma must have at least one other diagnostic criteria for NF1 as defined by the NIH Consensus Conference.

• Six or more cafe-au-lait spots (greater than 0.5 cm in prepubertal subjects or greater than 1.5 cm in postpubertal subjects)
• Freckling in the axilla or groin
• Optic glioma
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A first degree relative with NF1

Specific eligibility criteria stratum 1:

Disease status:

• Radiographic disease progression as defined for stratum 3 is not required for trial entry.

Patient does not have clinical symptoms from the plexiform neurofibroma.

Specific eligibility criteria stratum 2:

Disease status:

• Radiographic disease progression as defined for stratum 3 is not required for trial entry.
• Patient has clinical symptoms from the plexiform neurofibroma.

Specific eligibility criteria stratum 3:

Disease status:

• Patients must have a radiographically progressive plexiform neurofibroma(s) with or without clinical symptoms. Progression at the time of study entry is defined as:
• Presence of new plexiform neurofibromas on MRI within the last 12 months OR
• A measurable increase of the plexiform neurofibroma (greater than or equal to 20 percent increase in the volume, or a greater than or equal to 13 percent increase in the product of the two longest perpendicular diameters, or a greater than or equal to 6 percent increase in the longest diameter) over the last two consecutive scans (MRI or CT), or over the time period of approximately one year prior to evaluation for this study.

Surgery/Residual disease: Patients are only eligible if complete tumor resection is not feasible, or if a patient with a surgical option refuses surgery. Patients must have measurable residual tumor present. For the purpose of this study a measurable lesion will be defined as a lesion of at least 3 cm measured in one dimension. Evidence of recurrent or progressive disease is NOT necessary. Patients must be at least 21 days from surgery, if performed, prior to receiving their first dose of study drug.

Prior therapy: Since there is no standard effective chemotherapy for patients with progressive plexiform neurofibromas, patients may be treated on this trial without having received prior therapy. If patients have received prior therapy, they must have recovered from all toxic effects prior to entering this study.

Performance Status: Patients should have a life expectancy of at least 12 months and a Karnofsky or Lansky performance score of greater than or equal to 50. Patients who are wheelchair bound because of paralysis should be considered ambulatory when they are up in their wheel chair.

Organ Function: Subjects must have adequate hepatic, renal and bone marrow function as defined by the following parameters:

• An absolute granulocyte count greater than 1500/microL, a hemoglobin greater than 10 gm/dl, and a platelet count greater than 100,000/microL at study entry.
• Bilirubin less than 1.5 mg/dl and SGPT less than or equal to 2 times upper limit of normal.
• An age-adjusted normal serum creatinine (see below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73 m(2).
• Age less than or equal to 5, Maximum Serum Creatinine - 0.8 (mg/dl)
• Age greater than 5 to less than or equal to 10, Maximum Serum Creatinine - 1.0 (mg/dl)
• Age greater than 10 to less than or equal to 15, Maximum Serum Creatinine - 1.2 (mg/dl)
• Age greater than 15, Maximum Serum Creatinine - 1.5 (mg/dl)

Baseline Clinical and Radiographic Evaluations: MRI scan of the target plexiform neurofibroma(s), performed according to study requirements, including axial and coronal STIR images within 4 weeks of enrollment on study. Patients with orbital PNF's must have a baseline ophthalmologic evaluation as per Appendix G performed prior to study enrollment by an ophthalmologist familiar with the protocol guidelines. Patients with pain associated with the target PNF must be able to fill out the Pain Medication Diary with at least one week of documentation prior to study enrollment.

Informed Consent: All patients or their legal guardians (if the patients is less than 18 years old) must sign an IRB approved document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussion in order to obtain verbal assent.

EXCLUSION CRITIERIA:

Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate Pegintron or are likely to interfere with the study procedures or results.

An investigational agent within the past 30 days

Evidence of an optic glioma requiring treatment with chemotherapy or radiation therapy at the time of study entry

History of malignant peripheral nerve sheath tumor or other cancer other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ

Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, or immunotherapy

Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy

Severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease

Pre-existing severe psychiatric condition or a history of a psychiatric disorder requiring hospitalization or a history of suicidal ideation or attempt

Thyroid dysfunction not responsive to therapy

Uncontrolled diabetes mellitus

History of seropositivity for HIV

Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception

Subjects with a medical condition requiring chronic systemic corticosteroids

Subjects who are known to be actively abusing alcohol or drugs

Subjects who have not recovered from the effects of recent surgery

Prior administration of interferon alfa-2b or Pegintron