Imiquimod and Tumor Lysate Vaccine Immunotherapy in Adults With High Risk or Recurrent Grade II Gliomas

To determine the response rate and magnitude of CD8+ T-cell responses against the
Imiquimod/BTIC lysate-based vaccines in post-vaccine PBMC using IFN- ELISPOT. ELISPOT assays
indicate functional status of the antigen-specific T cells as cytokine-expression, and we are
particularly interested in Type-1 (i.e. IFN expressing) T cell response. Therefore, IFN
ELISPOT will be used as the primary assay for the immunological endpoint.

Using flow-cytometry, we will also evaluate the numbers of lymphocyte subsets such as CD4+ T
cells, CD4+/Foxp3+ regulatory T cells in an exploratory manner. In addition, in participants
who undergo surgical debulking of the progressing tumor, if the tumor tissue is available,
infiltration of antigen-specific CTLs will be evaluated by flow cytometry of
tumor-infiltrating lymphocytes with the Imiquimod/BTIC lysate-based vaccine-targeted GAA
specific MHC-tetramers. In addition, serological responses will be evaluated with
flow-cytometry of BTIC cells as well as western blotting. These plans (in this paragraph) are
immunological evaluations; however, do not compose the primary endpoints due to their
exploratory nature.

We will determine whether it is safe to administer Imiquimod/BTIC lysate-based vaccines in
patients with grade II gliomas. Endpoints will therefore include incidence and severity of
adverse events, using standard criteria as well as close clinical follow-up as would be
performed normally in this group of participants following vaccinations. All reported or
observed toxicities and adverse events at all clinic visits will be graded, documented and
reported according to a standard toxicity table, the Common Terminology Criteria for Adverse
Events (CTCAE) version 4.0

Inclusion Criteria:

- Cohort 1 and 2: Age ≥18 year old with histologically diagnosed World Health
Organization (WHO) grade II astrocytoma or oligoastrocytoma with "high-risk" factors -
defined as:

- age ≥ 40 with any extent resection;

- age 18-39 with incomplete resection (post-op MRI showing >1cm residual disease,
based on the maximum dimension of residual T2 or fluid-attenuated
inversion-recovery [FLAIR] abnormality from the edge of the surgical cavity
either laterally, anteroposteriorly, or superoinferiorly) or

- age 18-39 with neurosurgeon-defined gross total resection (GTR) but the tumor
size is ≥ 4 cm (the maximum preoperative tumor diameter, based on the axial
and/or coronal T2 or FLAIR MR images) Cohort 3: Age ≥18 year old with
histologically diagnosed WHO grade II glioma with recurrence

- Karnofsky performance status ≥ 60%

- Clinically stable and off corticosteroids for at least 4 weeks prior to study
enrollment

- Adequate organ function within 14 days of study registration including:

- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count
(ANC) ≥1.0 x 109/L, platelets ≥100 x 109/L; hemoglobin ≥ 8 g/dL

- Hepatic: - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age and SGPT
(ALT) ≤ 2.5 x upper limit of normal (ULN) for age

- Renal: Normal serum creatinine or creatinine clearance ≥60 ml/min/1.73 m2

Exclusion Criteria:

- History of immune system abnormalities such as hyperimmunity (e.g., autoimmune
diseases) that required systemic immunosuppression therapy and hypoimmunity (e.g.,
myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant
immunosuppression)

- Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g.
hypothyroidism)

- Any conditions that could potentially alter immune function (AIDS, multiple sclerosis,
diabetes, renal failure)

- Receiving ongoing treatment with immunosuppressive drugs, excluding those patients
requiring dexamethasone for treatment of tumor-related edema

- Currently receiving any investigational agents or registration on another therapy
based trial

- Pregnant or lactating