After informed consent has been signed, subjects who have not had a tetanus booster within
10 years will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria
Within 2 weeks of signing consent eligible subjects will undergo a 1-2 hour leukapheresis
(to pull off white blood cells) for immune monitoring and within 48 hours vaccine site
pre-conditioning will be performed as a single dose of Td toxoid (in a total volume of 0.4
mLs salt water/saline) given in the intradermal space (just under the surface of the skin)
12-24 hours prior to receiving PEPIDH1M vaccine in the same manner. The peptide vaccine is
administered in the upper thigh area approximately 4 inches below the groin in the
intradermal space as vaccine # 1. Subsequent vaccines will be given on day 15 3 days
(vaccine #2) and day 30 3 days (vaccine #3). All injections will alternate sides. These
injections will occur without temozolomide (standard of care chemotherapy).
Seven to 10 days after the 3rd vaccine, subjects will have peripheral blood work drawn for
immunologic monitoring. This will be followed by surgery to remove the tumor no less than 3
days and no longer than 7 days after the immunologic monitoring blood work. Tumor samples
will be evaluated for the IDH1 markers and analyzed for other cells that may have entered
Based on tissue obtained at surgery, subjects with stable histologic grade at recurrence
will then be treated with vaccine and temozolomide. During monthly cycles of temozolomide,
subjects will receive the vaccine on day 21 2 days. Patients that have transitioned to a
higher Grade brain tumor will not be eligible to continue and will be removed from the
study. All Adverse Events will be collected from time of consent until off study. For
purposes of this study, subjects will be considered off study 2 months after the last
vaccine. Subjects will be followed only for survival thereafter.
For immune monitoring, a final peripheral blood draw will be performed following 3 months of
temozolomide and vaccine therapy. Peripheral blood will also be drawn for immune monitoring
evaluation at progression, if possible.
For biomarker testing, subjects will have blood and urine collected during the following
times: prior to vaccine therapy (at consent or leukapheresis visit), prior to vaccine #3,
prior to surgery to remove the tumor, prior to discharge from hospital following the surgery
to remove the tumor, prior to each subsequent monthly vaccine administrations, and at
progression (if possible).
Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to
standard of care every 2 months 2 weeks while on temozolomide and afterward, per the
treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO)
criteria will be used for assessment of pseudoprogression and tumor progression. Subjects
demonstrating definitive progression will be removed from study.
As part of standard care for these subjects, upon tumor progression, participants may
undergo biopsy or resection. As this is not a research procedure, consent will be obtained
separately. Subjects that have this procedure done within the Duke University Health System
will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell
infiltration, antigen expression, and biomarkers for immunologic response.
1. Age 18 years.
2. IDH1R132H expression in tumor from initial diagnosis
3. Radiographic and/or clinical recurrent and resectable Grade II glioma.
4. Signed informed consent. If the subject's mental status precludes his/her giving
informed consent, written informed consent may be given by the responsible family
member or legal representative.
5. For females of child-bearing potential, negative serum pregnancy test 48 hours prior
to first treatment with temozolomide (TMZ) or vaccine.
6. Women of childbearing potential and male participants must agree to practice adequate
7. Karnofsky Performance Status (KPS) of 60.
8. Complete Blood Count (CBC)/differential with adequate bone marrow function to
tolerate TMZ and surgical resection as defined below within 2 weeks of enrollment:
- Absolute neutrophil count, 1500 cells/mm3.
- Platelet count, 100,000 cells/mm3.
- Hemoglobin 10 g/dl. (Note: the use of transfusion or other intervention to
achieve Hgb 10 g/dl is acceptable.)
9. Adequate renal function to tolerate TMZ and surgical resection as defined below
within 2 weeks of enrollment:
- Blood Urea Nitrogen (BUN) 25 mg/dl.
- Creatinine 1.7 mg/dl.
10. Adequate hepatic function to tolerate TMZ and surgical resection as defined below
within 2 weeks of enrollment:
- Bilirubin 2.0 mg/dl.
- Alanine Aminotransferase (ALT) 3 x normal range.
- Aspartate Aminotransferase (AST) 3 x normal range
1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease
free for 3 years. (For example, carcinoma in situ of the breast, oral cavity, and
cervix are all permissible.)
2. Metastases detected below the tentorium or beyond the cranial vault.
3. Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the
head and neck region (other than TMZ prescribed during radiation for glioma); note
that prior chemotherapy for a different cancer is allowable.
4. Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization.
- Transmural myocardial infarction within the last 6 months.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
note, however, that HIV testing is not required for entry into this protocol.
The need to exclude patients with AIDS from this protocol is necessary because
treatments involved in this protocol may be significantly immunosuppressive.
- Major medical illnesses or psychiatric impairments that in the investigator's
opinion will prevent administration or completion of protocol therapy.
- Active connective tissue disorders, such as lupus or scleroderma that in the
opinion of the treating physician may put the patient at high risk for radiation
5. Pregnant or lactating women, due to possible adverse effects on the developing fetus
or infant due to study drug.
6. Prior allergic reaction to temozolomide.
7. Patients treated on any other therapeutic clinical protocols within 30 days prior to
study entry or during participation in the study.
8. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any
component of Leukine.
9. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both