Vaccination-Dendritic Cells With Peptides for Recurrent Malignant Gliomas

This is a single-institution Phase I/II study designed to evaluate the safety, the induction
of an immune response, and the preliminary clinical response of vaccinations with Type-1 αDCs
(αDC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC
in patients with recurrent malignant gliomas. The hypothesis is that this form of vaccines in
combination with poly-ICLC treatment will prove to be safe, and will induce potent
anti-glioma immune responses.

The primary objective is to establish the safety of the approach.

The secondary objectives are to 1) assess the immunological response against GAAs in patients
with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using
enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays
and 2) assess the preliminary anti-tumor clinical activity of the vaccines as measured by
radiological response (MRI), overall survival, and four- and six-month progression-free
survival (PFS).

Inclusion Criteria:

- Patients must have a histologically confirmed

- recurrent glioblastoma (GBM)

- anaplastic astrocytoma (AA)

- anaplastic oligodendroglioma (AO)

- anaplastic mixed oligoastrocytoma (AMO)

- other anaplastic glioma

- Patients must have received prior external beam radiotherapy and/or chemotherapy
unless patients refused the options.

- Patients may have had treatment for no more than 2 prior relapses. Relapse is defined
as progression following initial therapy (i.e. radiation +/- chemo if that was used as
initial therapy).

- Patients must be HLA-A2 positive.

- All patients must sign an informed consent document indicating that they are aware of
the investigational nature of this study.

- Patients must sign an authorization for the release of their protected health
information.

- Patients must be > 18 years old, and with a life expectancy > 8 weeks. -Patients must
have a Karnofsky performance status of > 60.

- Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any
investigational agent, 4 weeks from prior cytotoxic therapy and/or at least two weeks
from vincristine, 4 weeks from nitrosoureas, 3 weeks from procarbazine administration,
and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide,
cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the
definition of non-cytotoxic agents should be directed to the principal investigator.

- Patients must not have any disease that will obscure toxicity or dangerously alter
drug metabolism.

- Patients must not have any serious concurrent medical illness.

- Documented negative serum beta-HCG for female patients of child-bearing age.

- Patients must be free of systemic infection. Subjects with active infections (whether
or not they require antibiotic therapy) may be eligible after complete resolution of
the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7
days before beginning treatment.

- Patients must have adequate organ function as measured by:

1. Hematopoietic:

- granulocytes at least 2500/mm3

- lymphocytes at least 1000/mm3

- platelets at least 100,000/mm3

- hemoglobin at least 10.0 g/dL

2. Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction
at rest must be at least 50% or within the normal range of the institution. A
cardiology clearance will be required for LV ejection fraction 50%.

3. Hepatic: AST, ALT, GGT, LDH, Alk phos within 2.5 x upper normal limit and total
bilirubin no greater than 2.0 mg/dL.

4. Renal: Serum creatinine up to 1.5 x upper normal limit.

5. Pretreatment baseline evaluations for laboratory parameters must be obtained
within 10 to 18 days of subject registration.

Exclusion Criteria:

- Pregnant or breast-feeding.

- Presence of metastatic disease.

- Active bacterial, viral or fungal infections. Subjects with active infections (whether
or not they require antibiotic therapy) may be eligible after complete resolution of
the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7
days before beginning treatment.

- Chemotherapy, biologic therapy or radiation therapy less than one month prior to study
entry.

- History or presence of autoimmune disease.

- Use of immunosuppressives within 4 weeks prior to study entry or anticipated use of
immunosuppressive agents. Minimum doses of corticosteroid (dexamethasone up to 4
mg/day) is permitted.

- Subjects with uncontrolled pain. -Subjects who have sensitivity to drugs to provide
local anesthesia.