Gliomatosis Cerebri Clinical Trials

• Age: Patients must be less than 22 years at the time of enrollment; there is no lower age limit.

• All participants must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the NIH Consensus Conference criteria.

• Diagnosis: LGG (WHO Grade 1 and 2) of the brain and spinal cord are eligible. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings. Biopsy for histologic diagnosis is required if there is clinical suspicion for a high-grade tumor; special attention is recommended in older adolescents or young adults to the potential for malignant transformation. Patients with metastatic disease are eligible.

• Patients must meet at least one of the following criteria for progression or recurrence of a previously treated target tumor:

∙ Progression or recurrence on MRI.

‣ New or worsening neurologic symptoms attributable to the target tumor.

‣ For patients with OPG: visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year by examination or history, attributable to tumor.

• Measurable Disease: Patients must have two-dimensional measurable tumor \>1cm2.

• Prior Therapy: Patients must have had at least one prior medical treatment for the target LGG.

• Performance Level: Patients must have a performance status of equal or \> than 50 using Karnofsky for patients equal or ≥ 16 years of age and Lansky for patients \< 16 years of age.

• Patients must have recovered to grade ≤1 from any acute toxicities from all prior treatments. to enroll on this study and meet time restrictions from end of prior therapy as defined below:

∙ Myelosuppressive chemotherapy: must have received the last dose of myelosuppressive therapy at least 4 weeks prior to study registration, or at least 6 weeks if nitrosourea.

‣ Investigational/biological agent: Patient must have received the last dose of other investigational, immunotherapy, or biological agent \> 14 days prior to study registration or at least 5 half-lives, whichever is greater. Bevacizumab last dose \> 36 days prior to enrollment.

‣ Radiation therapy: Patients SHOULD NOT have received prior irradiation.

‣ Study specific limitations on prior therapy: There is no limit on the number of prior treatment regimens.

‣ Growth factor(s): Must not have received any hematopoietic growth factors within 7 days of study entry or \> 14 days if pegylated GCSF is used.

‣ Prior surgery: At the time of enrollment, must be ≥ 3 weeks from prior major surgery such as craniotomy, orthopedic surgery, abdominal surgery or ≥1 week from minor surgery and completely recovered. Port or central line placement is not considered a major surgery.

• Organ Function Requirements:

• All patients must have adequate organ function defined as:

‣ 1 Hematologic Function:

‣ Hemoglobin: \> 8.0 gm/dl (may transfuse PRBCs)

‣ ANC: \> 750/mm3. Must be at least 7 days after last dose of growth factor or \> 14 days since last dose of pegylated GCSF

‣ Platelet Count: \> 75,000/mm3 (transfusion independent; ≥ 7 days from last transfusion)

‣ 2 Renal Function: Serum creatinine which is less than 1.5 times ULN for age (as per the table below) or GFR \> 70 ml/min/1.73m2

• Renal Function Normal for Age

• Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to \< 6 months 0.4 0.4 6 months to \< 1 year 0.5 0.5 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4

• ≥ 16 years 1.7 1.4

• Liver Function:

‣ Total bilirubin \< 1.5 x ULN (Children with diagnosis of Gilbert's Syndrome will be allowed on the study regardless of their total and indirect bilirubin levels as long as the direct bilirubin is less than 3.1 mg/dL.)

‣ SGPT (ALT) ≤ 5 x ULN

‣ SGOT (AST) ≤ 5 x ULN

• Pulmonary Function:

• No evidence of dyspnea at rest, and a pulse oximetry ≥ 92%.

• Reproductive Function:

• Female patients of childbearing potential must have negative serum or urine pregnancy test within 7 days prior to the first dose of poly-ICLC. Patient must not be pregnant or breast-feeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, including abstinence, while being treated on this study and for 90 days following cessation of treatment.

⁃ Patient is able to start treatment within 7 days after enrollment.

⁃ Patients with neurological deficits must be stable for a minimum of 1 week prior to enrollment.

⁃ Patients are only eligible if complete resection of the LGG with acceptable morbidity is not feasible, or if a patient with a surgical option refuses surgery.

⁃ Parents/legal guardians must provide written informed consent and agree that they will comply with the study.