Summary

This phase II trial tests whether poly ICLC works to shrink low-grade gliomas that are growing, spreading, or getting worse (progressive) or that have come back (recurrent) in children and young adults with neurofibromatosis type 1. Poly ICLC, made from ribonucleic acid (RNA), may help the body build an effective immune response to kill tumor cells. Giving poly ICLC may help decrease the size of low-grade gliomas in patients with neurofibromatosis type 1.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate the efficacy of poly-ICLC in pediatric neurofibromatosis type 1 (NF1) patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (complete response [CR] + partial response [PR]) within the first 48 weeks (12 cycles) of therapy.

SECONDARY OBJECTIVES:
I. Determine 12, 24 and 60 month progression free survival (PFS) in pediatric NF1 patients with progressive LGG treated with poly-ICLC.
II. Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by best objective tumor response rate (CR+PR) within 24 cycles of therapy.
III. Evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive LGG as measured by clinical benefit response rate (CR+PR + minor response [MR] + stable disease [SD]) after 12 and 24 cycles of therapy.
IV. Assess the toxicity associated with poly-ICLC treatment in pediatric NF1 patients with LGG.

EXPLORATORY OBJECTIVES:
I. Evaluate the visual outcome measures in children with progressive optic pathway gliomas treated with poly-ICLC.
II. Evaluate patient reported outcomes and quality of life measures.
III. Evaluate biological correlates.
IV. Compare Response Assessment in Neuro-Oncology (RANO) and Response Assessment in Pediatric Neuro-Oncology (RAPNO) response determinations in this population.

OUTLINE:
Patients receive poly ICLC intramuscularly (IM) twice weekly (BIW) (Monday/Thursday or Tuesday/Friday). Treatment repeats every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patient undergo magnetic resonance imaging (MRI), and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for 5 years.

Eligibility

1. Patients must be less than 22 years at the time of enrollment; there is no lower age limit
2. All participants must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the National Institutes of Health (NIH) Consensus Conference criteria
3. LGG (World Health Organization [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
4. Patients must meet at least one of the following criteria for progression or recurrence of a previously treated target tumor: * Progression or recurrence on magnetic resonance imaging (MRI) * New or worsening neurologic symptoms attributable to the target tumor * For patients with optic pathway glioma (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
5. Patients must have two-dimensional measurable tumor > 1 cm^2
6. Patients must have had at least one prior medical treatment for the target LGG
7. 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
8. 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 granulocyte colony stimulating factor (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
9. Hemoglobin: >= 8.0 gm/dl (may transfuse packed red blood cells [PRBCs])
10. Absolute neutrophil count (ANC): >= 750/mm^3. Must be at least 7 days after last dose of growth factor or > 14 days since last dose of pegylated GCSF
11. Platelet Count: >= 75,000/mm^3 (transfusion independent; >= 7 days from last transfusion)
12. Serum creatinine which is less than 1.5 times upper limit of normal (ULN) for age (as per the table below) or glomerular filtration rate (GFR) > 70 ml/min/1.73 m^2 * Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male); 0.4 (female) * Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male); 0.5 (female) * Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male); 0.6 (female) * Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female) * Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female) * Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female) * Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female) * Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
13. 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.)
14. Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN
15. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 5 x ULN
16. No evidence of dyspnea at rest, and a pulse oximetry >= 92%
17. Female patients of childbearing potential must have a 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
18. Patient is able to start treatment within 7 days after enrollment
19. Patients with neurological deficits must be stable for a minimum of 1 week prior to enrollment
20. 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
21. Patients and/or parents/legal guardians must provide written informed consent and agree that they will comply with the study