A Study of ICT-121 Dendritic Cell Vaccine in Recurrent Glioblastoma

Immunotherapy holds promise in oncology for the potential to provide targeted anti-tumor
therapy with minimal adverse events. The goal of this study is to assess immunotherapy
directed to CD133 in an autologous dendritic cell product called ICT-121. CD133 antigen is
overexpressed on many types of cancer cells and is associated with shortened survival. CD133
positive cancer stem cells are resistant to chemotherapy. Patients with recurrent
glioblastoma who have the HLA A2 phenotype will receive autologous vaccine of DC pulsed with
purified peptides from CD133.

Approximately 20 patients with any recurrence of glioblastoma multiforme (GBM) will be
treated. After informed consent and screening, patients will undergo apheresis to collect
peripheral blood mononuclear cells (PBMCs). Monocytes will be purified and cultured into
dendritic cells (DC) that are pulsed with purified peptides from CD133 antigen. The pulsed
dendritic cells will then be aliquoted and frozen. Patients will have the autologous DCs
reinfused intradermally. Patients will receive at least four intradermal injections of the
autologous DC vaccine and additional vaccines during a maintenance phase. The goal is to
induce a cytotoxic T cell response to CD133 positive cells. The primary objective of the
study is to assess safety and tolerability. Clinical response rates will be monitored as well
as the immune responses to CD133.

Inclusion Criteria:

1. Any recurrence of a glioblastoma multiforme

2. ≥ 18 years of age

3. Human leukocyte antigen HLA A2 positive

4. Karnofsky Performance Score (KPS) of ≥ 70%

5. Baseline hematologic studies and chemistry profiles must meet the following criteria:

- hemoglobin (Hgb) > 9.9 g/dL

- absolute neutrophil count (ANC) > 1000/mm3

- platelet count > 100,000/mm3

- blood urea nitrogen (BUN) < 30 mg/dL

- creatinine < 2 mg/dL

- alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 4x upper limit of normal (ULN)

- prothrombin time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6 x
control unless therapeutically warranted

6. Female patients of child bearing potential must have negative serum pregnancy test

7. If not surgically sterile, male and female patients of childbearing age must use
double barrier contraception (hormonal; intrauterine device; barrier)

8. Written informed consent, Release of Medical Records Form and HIPAA reviewed and
signed by patient or legally authorized representatives

9. Ability to understand and the willingness to sign a written informed consent document.

10. Any Grade 3 or 4 toxicities (according to NCI CTCAE) resolved for at least 2 weeks
prior to first treatment

Exclusion Criteria:

1. Radiosurgery including Gamma Knife, linear accelerator based radiosurgery, CyberKnife
and placement of Gliadel wafer

2. Presence of any other active malignancy or prior history of malignancy, except for:
basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate
carcinoma not requiring active treatment

3. New York Heart Association >/= Grade 3 congestive heart failure within 6 months prior
to study entry

4. Uncontrolled or significant cardiovascular disease, including:

- Myocardial infarction and transient ischemic attack or stroke within 6 months
prior to enrollment

- Uncontrolled angina within 6 months

- Diagnosed or suspected congenital long QT syndrome

- Any history of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);

- Clinically significant abnormality on electrocardiogram (ECG)

5. Pulmonary disease including or greater than grade 2 dyspnea or laryngeal edema, grade
3 pulmonary edema or pulmonary hypertension according to CTCAE 4.03

6. Severe acute or chronic medical or psychiatric condition that could increase the risk
associated with trial participation or trial drug administration or could interfere
with the interpretation of trial results and, in the judgment of the investigator,
would make the patient inappropriate for entry into the trial. This includes but is
not limited to the following:

1. Immunosuppressive disease

2. Chronic renal disease / failure

3. Concurrent neurodegenerative disease,

4. Dementia or significantly altered mental status that would prohibit the
understanding or rendering of informed consent and compliance with the
requirements of the protocol.

7. Presence of an acute infection requiring active treatment with antibiotics/antivirals;
prophylactic administration is allowed

8. Known history of an autoimmune disorder

9. Known human immunodeficiency virus positivity or acquired immunodeficiency syndrome
related illness or other serious medical condition

10. Breastfeeding

11. Received any other therapeutic investigational agent within 30 days of screening,
except for immunotherapy. Patients with previous immunotherapy are not eligible
regardless of timing.

12. Contraindication to MRI

13. Foreseeable condition which would preclude the reduction of steroids (dexamethasone)
to a maximum of 2 mg BID within a week prior to apheresis -