A Pilot Study of Glioma Associated Antigen Vaccines in Conjunction With Poly-ICLC in Pediatric Gliomas

Eligibility Criteria

*Tumor Types - Tumor type/location:

Stratum A: Newly diagnosed diffuse intrinsic pontine gliomas OR any biopsy proven high-grade glioma* involving the brainstem. Patients may not have received chemotherapy during or after radiation. Patients must be registered within 4-12 weeks of completing radiation.

Stratum B: Newly diagnosed, non-brainstem high-grade glioma* Patients may not have received chemotherapy during or after radiation. Patients must be registered within 4-12 weeks of completing radiation.

Stratum C: Unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Patients may not have received radiation to the index lesion within 1 year of enrollment.

Stratum D: Non-brainstem high-grade gliomas* that have recurred following treatment.

Stratum E: Newly diagnosed high-grade gliomas* or brain stem gliomas who received chemotherapy during radiation therapy. Patients may not have received chemotherapy after radiation therapy was completed. Patients must be registered within 4-12 weeks of completing radiation.

Stratum F: Newly diagnosed high-grade gliomas with metastatic disease within the CNS requiring craniospinal radiation therapy. Patients may or may not have received chemotherapy during radiation, but cannot have received chemotherapy after radiation therapy was completed. Patients must be registered within 4-12 weeks of completing radiation.

• Eligible histologies include glioblastoma (GBM), anaplastic astrocytoma (AA) or gliosarcoma. Patients with any oligodendroglioma component are NOT eligible.
• HLA-A2 positive based on flow cytometry.
• Patients in Stratum A B and E must have received standard involved field radiation therapy [RT] defined as fractionated external beam radiotherapy with total doses between 5000-6000 cGy. Patients in these strata must be registered within 4-12 weeks of completing RT.
• Patients in Stratum F must have received craniospinal radiation.
• Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day, max 4 mg/day Dexamethasone) corticosteroid for at least one week prior to study registration.
• All patients must sign an IRB-approved informed consent document
• Patients must be ≥ 12 months and <22 years of age at the time of study registration.
• Patients must have a performance status of ≥ to 60; (Karnofsky if > 16 years and Lansky if ≤ 16 years of age.
• Patients must have life expectancy of at least 8 weeks.
• documented negative serum βHCG for female patients who are post-menarchal. Because the effect of the peptide-based vaccine and poly-ICLC on the fetus has not sufficiently been investigated, pregnant females will not be included in the study. Males and females must agree to use effective birth control methods during the course of vaccination (from the first vaccine to two weeks after the last vaccine). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the peptide-based vaccine and poly-ICLC, breastfeeding should be discontinued if the mother is treated in this study.
• Patients must be free of systemic infection at the time of registration. Patients on IV antibiotic therapy must be off IV antibiotics for at least 7 days prior to registration.
• Patients with adequate organ function as measured by: Bone marrow: ANC > 1,000/µl; Platelets > 100,000/µl (transfusion independent); absolute lymphocyte count of ≥500/uL; Hemoglobin >8 g/dl (may be transfused). Hepatic: bilirubin ≤ 1.5x institutional normal for age; SGPT (ALT) < 3x institutional normal.

Renal: Serum creatinine based on age or Creatinine clearance or radioisotope GFR >70 ml/min/ml/min/1.73 m²

• Patients on Strata C and D must have recovered from the toxic effects of prior therapy: at least 3 weeks form the last dose of standard cytotoxic chemotherapy or myelosuppressive biological therapy and at least 1 week from the last dose of non-myelosuppressive biologic therapy. Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator.

• No overt cardiac, gastrointestinal, pulmonary or psychiatric disease.

  • Exclusion Criteria

3.2.1 Presence of metastatic disease for patients in Stratum A, B, D and E. Patients with low grade gliomas (stratum C) may have tumor spread within the CNS. Patients in Stratum F must have tumor spread within the CNS.

3.2.2 Patients enrolled in Strata A and B may not have received any prior chemotherapy or anti-glioma therapy of any type other than radiation therapy (see 3.1.3) Patients enrolled on stratum C must have received at least two prior chemotherapy or biologic therapy regimens and may not have received radiation to the index lesion within 1 year of enrollment. Patients on Strata A, B, E, and F can not have received chemotherapy after radiation therapy was completed.

3.2.3 Concurrent treatment or medications (must be off for at least 1 week) including:

• Interferon (e.g. Intron-A®)
• Allergy desensitization injections
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational therapeutic medication

3.2.4 Patients must not have a history of, or currently active autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement.

3.2.5 Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents. Dexamethasone, or other corticosteroid medications, if used in the peri-operative period and/or during radiotherapy, must be tapered (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) for at least one week before study registration. Topical corticosteroids are acceptable.

3.2.6 Patients with known addiction to alcohol or illicit drugs.

3.2.7 Because patients with immune deficiency are not expected to respond to this therapy, HIV-positive patients are excluded from the study.

3.3 Start of Treatment

3.3.1 Patients must be registered prior to the start of treatment.

3.3.2 The date protocol therapy is projected to start must be no later than 7 days after the date of study registration.