A Bi-Institutional Pilot Study of Vaccinations for Patients with Low Grade Glioma

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DESCRIPTION (provided by applicant): This is a bi-institutional pilot study between the University of Pittsburgh Cancer Institute and the Comprehensive Cancer Center of Wake Forest University of a vaccination regime (subcutaneous injections of glioma-associated antigen [GAA]-derived cytotoxic T-lymphocyte [CTL] epitope-peptides with simultaneous intramuscular [i.m.] administration of poly-ICLC) that is designed to efficiently induce anti-tumor T-cell responses in adults with either World Health Organization (WHO) grade II astrocytoma or oligoastrocytoma with poor prognostic factors. The overall objective of this pilot study is to collect immunological and safety data to decide whether a larger study of clinical efficacy is warranted. Unfavorable subsets of adult patients with supratentorial low grade glioma (LGG) are defined as ones with astrocytoma or oligoastrocytoma histology and either one of the following conditions: 1) age e 40 with any extent resection; 2) age 18-39 with incomplete resection, or 3) age 18-39 with neurosurgeon- defined gross total resection but the tumor size is e 4 cm in diameter. These patients have as high as an 89% risk of suffering disease recurrence at 5 years following surgery. However, the slower growth rate of LGG (in contrast to malignant gliomas) should allow sufficient time to administer multiple immunizations, which may lead to the induction of high levels of GAA-specific immunity. Because patients with LGG are likely not to be as immune-compromised as patients with higher-grade gliomas, they may exhibit greater immunological responses. In addition, poly-ICLC has been demonstrated to enhance the vaccine effects in preclinical brain tumor models, and to be safe in malignant glioma patients. Therefore, we hypothesize that this form of vaccine in combination with poly-ICLC treatment will safely induce potent anti-glioma immune response. Participants will be treated with s.c. injections of GAA-vaccines every 3 weeks for 8 times and poly-ICLC will be administered (20 <g/kg i.m.) on the day of and on day 4 after each vaccine. Participants will be evaluated for any possible adverse event, regimen limiting toxicity (RLT), and clinical response by clinic visits and MR imaging. Participants who demonstrate any immunological response without RLT or tumor progression may undergo additional vaccinations. We will also be keen discerning whether the patient's prior (postoperative) radiation therapy (RT) can influence the safety of, and immune responses against the proposed vaccines. To this end, we will stratify patients with "high risk" LGG into two cohorts based on whether patients received postoperative RT. We will treat a total of 18 patients (9 patients/cohort) with two Specific Aims that will determine: 1) induction of GAA-specific CD8+ T cell responses, and 2) safety with an early stopping rule based on the frequency of RLT in each cohort. Data from this pilot study will allow us to determine whether a subsequent lager trial is warranted. PUBLIC HEALTH RELEVANCE: This is a bi-institutional pilot study between the University of Pittsburgh Cancer Institute and the Comprehensive Cancer Center of Wake Forest University of a vaccination regime (subcutaneous injections of glioma-associated antigen-derived cytotoxic T-lymphocyte epitope-peptides with simultaneous intramuscular administration of poly-ICLC) that is designed to efficiently induce anti-tumor T-cell responses in adults with World Health Organization grade II astrocytoma or oligoastrocytoma with poor prognostic factors. The overall objective of this pilot study is to collect immunological and safety data that will be used to decide whether a larger study of clinical efficacy is warranted.