A Trial of Poly-ICLC in the Management of Recurrent Pediatric Low Grade Gliomas
Condition: Brain Tumors
MeSH terms: Glioma; Brain Neoplasms
Intervention: Poly ICLC
Intervention description: Children will receive poly-ICLC 20 mcg/kg twice weekly IM (using Monday/Wednesday schedule if possible). The first 2 doses will be administered in the clinic under supervision.
Intervention MeSH terms: Poly ICLC
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: glioma; pediatrics; cancer; brain tumor; low grade glioma

Summary:

      This study is for patients up to 21 years of age who have a tumor called a low grade glioma
      of the central nervous system (brain and spinal cord). The tumor has grown despite attempts
      to control it with chemotherapy or radiation. Low grade gliomas are a group of tumors that
      tend to grow slowly and could be cured if every bit of the tumor were surgically removed.
      These tumors are called Grade I or II astrocytomas.

      These tumors often grow in parts of the brain that prevent total removal without devastating
      neurologic complications or death. Although some low grade gliomas never grow, most will and
      are treated with either chemotherapy or radiation. There is good data showing that the growth
      of most low grade gliomas can be controlled with chemotherapy or radiation. However, some low
      grade gliomas in children and young adults grow despite these treatments. Poly-ICLC is a new
      drug that has been used safely in children and adults with different types of brain tumors.
      Earlier studies showed that this drug worked better for children and young adults with low
      grade gliomas than for children with more aggressive brain tumors. The main purpose of this
      study is to use Poly-ICLC treatment in a larger number of patients to see how well it works
      and how many side effects occur.

      As Poly-ICLC is not FDA approved, this study is authorized to use it under Investigational
      New Drug (IND)# 43984, held by Oncovir.

      Subjects will get injections of Poly-ICLC into muscle two times weekly. The first treatments
      will be given in the clinic so allergic or other severe reactions, if any, can be monitored.
      If subjects tolerate the injections and don't have a severe reaction, then the rest of the
      injections will be given at home. Subjects/caregivers will be trained to give injections.

      Treatment will last for about 2 years. Subjects may stay on treatment for longer than 2 years
      if their tumor shrinks in response to the injections, if study doctors think it is safe, if
      subjects want to remain on treatment, and if Poly-ICLC is available.

      Risks: Poly-ICLC has been used safely in children and adults at the dose used in this study,
      and at higher doses. Frequently seen side effects include irritation of the skin at the
      injection site and mild flu-like symptoms. These are usually relieved or avoided by use of
      over-the-counter medicines like acetaminophen (Tylenol).
    

Eligibility criteria:

        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 World Health Organization (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 not otherwise specified (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 MRI 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. Radiation therapy (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

          2. Absolute neutrophil count (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/Glomerular
        filtration rate (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 Upper limit of Normal (ULN) for age, AND

          2. alanine transaminase (ALT) < 2.5x ULN

          3. aspartate aminotransferase (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 prothrombin time (PT) and Partial thromboplastin time (PTT) at enrollment per
        institutional range

        Reproductive Function:Due to potential teratogenic effects of (poly-ICLC), negative serum
        beta-human chorionic gonadotropin (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.