Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of adjuvant temozolomide plus combined allogeneic
tumor primary tumor culture lysate / autologous dendritic cell (DC) vaccination (malignant
glioma tumor lysate-pulsed autologous dendritic cell vaccine) in newly diagnosed glioblastoma
patients following surgical debulking and external beam radiation therapy with concurrent
temozolomide.

SECONDARY OBJECTIVES:

I. To document survival and progression-free survival in newly diagnosed glioblastoma
patients receiving adjuvant temozolomide plus allogeneic tumor primary tumor culture lysate /
autologous DC vaccination to historical data.

TERTIARY OBJECTIVES:

I. Determine the ability of allogeneic tumor primary tumor culture lysate / autologous DC
vaccine to generate multiple tumor-associated antigens (TAA)-specific immune responses in
newly diagnosed glioblastoma multiforme (GBM) patients.

II. Assess the relationship between ability tumor induce TAA-specific immune responses and
evidence of immunosuppression (peripheral blood immunophenotyping by flow cytometry)
following allogeneic tumor primary tumor culture lysate / autologous DC vaccine in newly
diagnosed GBM patients.

III. Assess the relationship between efficacy endpoints (survival, progression-free survival,
tumor response) and tumor-associated antigen immune response following combined autologous or
allogeneic tumor lysate / DC vaccination and adjuvant temozolomide.

IV. Assess the relationship between efficacy endpoints (survival, progression-free survival,
tumor response) and evidence of immunosuppression at baseline and over time with combined
autologous or allogeneic tumor lysate / DC vaccination and adjuvant temozolomide.

OUTLINE:

COURSE 1: Patients receive temozolomide orally (PO) daily on days 1-5.

COURSES 2-3: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor
lysate-pulsed autologous dendritic cell vaccine intradermally (ID) on days 1, 3, and 5.

COURSES 4-6: Patients receive temozolomide PO daily on days 1-5 and malignant glioma tumor
lysate-pulsed autologous dendritic cell vaccine ID on day 1.

COURSES 7-12: Patients receive malignant glioma tumor lysate-pulsed autologous dendritic cell
vaccine ID on day 1.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Willing and capable of undergoing apheresis for collection of mononuclear cells

- Histologically confirmed GBM (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

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

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

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

- Hemoglobin (HgB) >= 9.0 g/dL

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

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

- Creatinine =< 1 x UNL

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

- Ability to understand and willingness to sign a written informed consent

- Willing to return to Mayo Clinic Rochester 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

- Completed standard external beam radiation with temozolomide

- Achieved a gross total or sub-total resection at time of surgery

Exclusion Criteria:

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

- Any of the following

- Pregnant women

- Nursing women

- Men or women 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 including treated lower grade gliomas; EXCEPTIONS:
non-melanotic skin cancer, carcinoma-in-situ of the cervix, or lower grade glioma that
has never been treated previously; 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)