A Trial of Poly-ICLC in the Management of Recurrent Pediatric Low Grade Gliomas

Inclusion Criteria:

• Age:Patients must be between 0 - 21 years of age when registered on this protocol.
• Diagnosis:Patients must have pathologically confirmed low grade glioma with histologic subtypes interpreted as WHO grade I and II including:
• juvenile pilocytic astrocytoma (JPA)
• pleomorphic JPA
• diffuse astrocytoma (fibrillary, gemistocytic, giant cell, or pleomorphic xanthoastrocytoma)
• low grade oligoastrocytoma
• low grade oligodendroglioma
• low grade glioma NOS Tumors of all regions of the CNS, with appropriate histology are eligible for study. However patients with tumors intrinsic to the optic nerve and involvement of the optic nerve cannot be biopsied/resected are eligible without histological confirmation.

Patients with neurofibromatosis type 1(NF1) are also eligible.

Patients must have demonstrated either tumor progression or recurrence by radiographic criteria and/or clinical criteria as defined below:

1. Patients with progressive non-resectable disease regardless of location in the brain or spine are eligible for this study. Patients with evidence of leptomeningeal dissemination are eligible for this study. Patients do not require biopsy/histologic confirmation at the time of progression or relapse.
2. Radiographic progression is defined as >40% increase in the product of the three perpendicular diameters of initial tumor relative to the initial baseline measurement - length (L)x width (W) x transverse (T) (current scan) > 1.4 x L x W x T (initial scan), or the development of any new sites of disease independent of the response of the initial tumor. See section 7.1.2 for methodology for tumor measurement.
3. Post radiation changes are often seen on post-treatment imaging studies, so that classification of a patient as having progressive disease may require several serial MRI's if the child has received radiation within the preceding 12 months.
4. Tumor volume includes the entire tumor volume seen on gadolinium enhanced T1 MR imaging plus non-enhancing abnormality seen on T2 or FLAIR.
5. All tumor cysts will be included in the tumor volume
6. Clinical progression without radiographic progression includes children with optic pathway gliomas who demonstrate sustained decrease in visual fields and/or acuity in three serial vision examinations. Each of the vision examinations must be performed >2 weeks apart.
7. Children with previously negative cerebrospinal fluid (CSF) cytology who show evidence of tumor cells in fluid obtained by lumbar puncture can be designated as having progressive disease in the absence of radiographic evidence of progression.

Measurable disease: Patients must have measurable disease documented by radiographic criteria prior to enrollment.

Performance Level and Life Expectancy:Patients must have a performance status of > 50% (Appendix I). Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. Patients must have a life expectancy of ≥ 8 weeks.

Prior Therapy:Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet time restrictions from end of prior therapy as stated below:

1. Myelosuppressive chemotherapy patients must have received the last dose of myelosuppressive therapy at least 3 weeks prior to study registration or at least 6 weeks if nitrosourea.
2. Investigational / Biological agent: Patient must have received the last dose of other investigational or biological agent >7 days prior to study registration
3. XRT: Patients must be ≥ 8 weeks since the completion of radiation therapy.
4. Study specific limitations on prior therapy: There is no limit on the number of prior treatment regimens or received doses of radiation therapy.
5. Growth factor(s): Must not have received any hematopoetic growth factors within 7 days of study entry or 21 days for neulasta.
6. Prior Surgery: Must be ≥ 2 weeks from prior surgery.
7. Steroids: Must be on a stable steroid dose for 7 days prior to study entry.

Organ Function Requirements:All patients must have adequate organ function defined as:

Hematologic Function:

1. Hemoglobin: > 8.0 gm/dl (may transfuse PRBCs)
2. ANC: > 750/mm3 Must be at least 7days after last dose of growth factor
3. Platelet Count: > 50,000 (transfusion independent; ≥ 7 days from last transfusion)

Renal Function:

Serum creatinine ≤ 2 x normal for age (see below) or Creatinine clearance/GFR > 60 cc/min/1.73 m2 [Urine Creatinine (mg/dL)][Volume collected (ml)]/[Serum Creatinine 9mg/dL)][Hours x 60]

Age (years) Maximum Serum Creatinine (mg/dL)

≤ 5 0.8 > 5 & ≤ 10 1.0 > 10 & ≤ 15 1.2 > 15 1.5

Liver Function:

1. Total bilirubin < 1.5 x ULN for age, AND
2. SGPT (ALT) < 2.5x ULN
3. SGOT (AST) < 2.5x ULN

Pulmonary Function:

No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry ≥ 94% if there is clinical indication for determination.

Coagulation Function:

Normal PT and PTT at enrollment per institutional range

Reproductive Function:Due to potential teratogenic effects of (poly-ICLC), negative serum beta-HCG in females, and use of effective contraception in males and females of childbearing potential, IS REQUIRED.

Exclusion Criteria:

• Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.
• Patients receiving other experimental immunotherapy.
• Patients may not have fever (38.50C) within 7 days of enrollment.
• No concurrent XRT or chemotherapy is allowed.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.