a vaccine trial for low grade gliomas

Conditions: Low Grade Glioma

Summary: the study will assess the immunogenicity, safety and preliminary clinical efficacy of the glioma associated antigen (gaa)/tetanus toxoid (tt) peptide vaccine and poly-iclc in hla-a2+ children with unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. radiation therapy counts as one biologic regimen, but patients may not have received radiation to the index lesion within 1 year of enrollment.

patients will be treated with subcutaneous injections of gaa/tt-vaccines starting on week 0 and every 3 weeks thereafter for up to 8 cycles or until off-treatment criteria are met (section 4.6). i.m. poly-iclc will be administered (30ug/kg i.m.) immediately following the vaccine. poly-iclc should be administered i.m. within 3 cm of the peptide-injection site. to allow for flexibility with scheduling, the peptide vaccine and poly-iclc dose may be given within one week of the date that the vaccine and poly-iclc administration are due. patients will be evaluated for any possible adverse event, regimen limiting toxicity (rlt) as well as clinical/radiological responses by clinical visits and mri scanning. follow-up mris will be performed (weeks 6, 15 and 24).

Eligibility criteria:
inclusion criteria: tumor type * unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. radiation therapy counts as a biologic regimen. patients may not have received radiation therapy to the index lesion within 1 year of enrollment. patients may have tumor spread within the central nervous system (cns). * hla-a2 positive based on flow cytometry. * 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. * patients must be ≥ 12 months and \< 22 years of age at the time of hla-a2 screening. * patients must have a performance status of ≥ 70; (karnofsky if \> 16 years and lansky if ≤ 16 years of age. * documented negative serum beta-human chorionic gonadotropin (hcg) 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. * patients must be free of systemic infection requiring iv antibiotics at the time of registration. patients must be off iv antibiotics for at least 7 days prior to registration. * patients with adequate organ function as measured by: bone marrow: absolute neutrophil count (anc) \> 1,000/µ; platelets \> 100,000/µ (transfusion independent); absolute lymphocyte count of ≥ 500/µ; hemoglobin \>8 g/dl (may be transfused). hepatic: bilirubin \< 1.5x institutional normal for age; serum glutamate pyruvate transaminase (sgpt) \< 3x institutional normal. * renal: serum creatinine based on age or creatinine clearance or radioisotope glomerular filtration rate (gfr) ≥ 70 ml/min/ml/min/1.73 m² * patients must have recovered from the toxic effects of prior therapy to grade 1 or better. patients must be at least 3 weeks from 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. * no overt cardiac, gastrointestinal, pulmonary or psychiatric disease. exclusion criteria: * patients living outside of north america are not eligible. * patients may not have received radiation to the index lesion within 1 year of enrollment. * 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 * patients must not have a history of, or currently active autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. * 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 must be tapered to 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. * because patients with immune deficiency are not expected to respond to this therapy, hiv-positive patients are excluded from the study. * patients who have received prior immunotherapy.