Vaccine Therapy and Cytokine-Induced Killer Cells in Treating Patients With Recurrent Glioblastoma

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of malignant glioma tumor lysate-pulsed autologous
dendritic cell vaccine (autologous dendritic cell [DC] / allogeneic glioblastoma multiforme
[GBM] culture lysate vaccination) combined with autologous cytokine-activated killer cell
transfer in glioblastoma patients at first or second recurrence.

SECONDARY OBJECTIVES:

I. To document survival and progression-free survival in glioblastoma patients at first or
second recurrence receiving autologous DC / allogeneic GBM culture lysate vaccination
combined with autologous cytokine-activated killer cell transfer and compare to historical
data.

TERTIARY OBJECTIVES:

I. Determine the ability of autologous DC / GBM culture lysate vaccination combined with
autologous cytokine-activated killer cell transfer to generate multiple tumor-associated
antigen (TAA)-specific immune responses in GBM patients at first or second recurrence.

II. Assess the relationship between ability tumor induced TAA-specific immune responses and
evidence of immunosuppression (peripheral blood immunophenotyping by flow cytometry)
following autologous DC / allogeneic GBM culture lysate vaccination combined with autologous
cytokine-activated killer cell transfer in GBM patients at first or second recurrence.

III. Assess the relationship between efficacy endpoints (survival, progression-free survival,
tumor response) and tumor-associated antigen immune response following autologous DC /
allogeneic GBM culture lysate vaccination combined with autologous cytokine-activated killer
cell transfer.

IV. Assess the relationship between efficacy endpoints (survival, progression-free survival,
tumor response) and evidence of immunosuppression at baseline and over time with autologous
DC / allogeneic GBM culture lysate vaccination combined with autologous cytokine-activated
killer cell transfer.

OUTLINE:

Patients receive cytokine-induced killer cells intravenously (IV) over 1 hour on day 13 of
course 1. Patients also receive malignant glioma tumor lysate-pulsed autologous dendritic
cell vaccine intradermally (ID) on days 1, 3, and 5 of courses 2 and 3, and on day 1 of
subsequent courses. Treatment with malignant glioma tumor lysate-pulsed autologous dendritic
cell vaccine repeats every 21 days for up to 13 courses in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Inclusion Criteria:

- First or second recurrence of previously histologically confirmed glioblastoma (grade
4 astrocytoma)

- NOTE: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) may
be included, primitive neuroectodermal tumor (PNET) variants are excluded; grade
4 oligodendrogliomas or oligoastrocytomas are specifically excluded

- Prior craniotomy and gross total or sub-total resection of tumor at this recurrence

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

- Absolute neutrophil count (ANC) >= 1500/uL

- Monocytes >= 300/uL

- Platelets (PLT) >= 100,000/uL

- Hemoglobin (HgB) >= 9.0 g/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3
x ULN

- Creatinine =< 1.5 x ULN

- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only

- Ability to understand and willingness to sign written informed consent

- Willing to return to Mayo Clinic in Rochester, Minnesota for follow-up

- Willing to provide tissue and blood samples for mandatory correlative research
purposes

- Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to
registration

Exclusion Criteria:

- Prior treatment

- Current or prior treatment for this cancer with immunotherapy and/or any other
investigational agents

- Surgery =< 2 weeks prior to registration

- Radiotherapy =< 12 weeks prior to registration

- Treatment with bevacizumab or any cytotoxic chemotherapy =< 8 weeks prior to
registration

- Any of the following

- Pregnant persons

- Nursing persons

- Persons of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Immunocompromised patients (other than that related to the use of corticosteroids)
including patients known to be human immunodeficiency virus (HIV), human T-cell
lymphotropic virus (HTLV), hepatitis B (HepB), or hepatitis C (HepC) positive

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- History of other malignancy other than glioma

- EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or
systemic cancer that has been in documented remission for > 10 years

- NOTE: if there is a history or prior malignancy, they must not be receiving other
specific treatment for their cancer

- History of myocardial infarction =< 180 days (6 months), or congestive heart failure
requiring use of ongoing maintenance therapy for life-threatening ventricular
arrhythmias

- Active infection =< 5 days prior to registration or fever > 38 degrees Celsius (C) on
day of registration

- History of tuberculosis or positive purified protein derivative (PPD) test

- Inability or unwillingness to have magnetic resonance imaging (MRI) scans performed
(e.g. cardiac pacemaker-dependent)