The primary purpose of this study is to determine the maximum tolerated dose (MTD) of
MT-201-GBM (pp65CMV antigen monocytes) that will be administered to patients newly diagnosed
with a type of brain tumor called glioblastoma (GBM) that has an unmethylated MGMT
(O[6]-methylguanine-DNA methyltransferase) (MGMT) gene promoter.
The investigational vaccine (MT-201-GBM) in this study is made from a type of immune cell
called monocytes, which have been engineered to express a cytomegalovirus (CMV) protein.
The monocyte vaccines are made from the patient's own cells, which are collected through a
procedure called leukapheresis. During leukapheresis, the patient's blood is collected into a
machine that removes white blood cells and then returns the remainder of the blood back to
the individual. The leukapheresis procedure is not typically associated with any discomfort
or pain. The white blood cells collected from leukapheresis are used to generate the
patient's monocyte vaccine. After leukapheresis, patients receive standard radiation therapy
combined with temozolomide for about 6 weeks, followed by one cycle of temozolomide for 21
days. About 2 days later, patients will receive the first monocyte vaccine, followed by 2
more monocyte vaccines every 4 weeks.
Inclusion Criteria:
- Age ≥18 years of age
- Glioblastoma patient with definitive resection prior to enrollment, with residual
radiographic contrast enhancement on most recent computed tomography (CT) or magnetic
resonance imaging (MRI) of <1 cm in maximal diameter in any axial plane
- Karnofsky Performance Status (KPS) score ≥ 70
- MGMT promoter unmethylated (Determined by Caris Life Science pyrosequencing)
- Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥
100,000 cells/µl prior to starting TMZ cycle 1 (patient must meet these criteria
within 4 weeks after the end of XRT/TMZ to be eligible)
- Serum creatinine ≤ 3 times institutional upper limit of normal (ULN) for age, serum
aspartate aminotransferase (AST) ≤ 3 times institutional ULN for age
- Bilirubin ≤ 1.5 times ULN prior to starting TMZ cycle 1 (Exception: Patient has known
Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional
lab testing of direct and/or indirect bilirubin supports this diagnosis. In these
instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
- Signed informed consent approved by the Institutional Review Board (IRB)
- Female patients must not be pregnant or breast-feeding. Female patients of
childbearing potential (defined as < 2 years after last menstruation or not surgically
sterile) must use a highly effective contraceptive method (allowed methods of birth
control, [i.e. with a failure rate of < 1% per year] are implants, injectables,
combined oral contraceptives, intra-uterine device [IUD; only hormonal], sexual
abstinence or vasectomized partner) during the trial and for a period of > 6 months
following the last administration of trial drug(s). Female patients with an intact
uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy
test within 48 hours prior to first study treatment.
- Fertile male patients must agree to use a highly effective contraceptive method
(allowed methods of birth control [i.e. with a failure rate of < 1% per year] include
a female partner using implants, injectables, combined oral contraceptives, IUDs [only
hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of
> 6 months following the last administration of trial drugs.
Exclusion Criteria:
- Pregnant or breast-feeding
- Women of childbearing potential and men who are sexually active and not willing/able
to use medically acceptable forms of contraception
- Patients with known potentially anaphylactic allergic reactions to gadolinium-DTPA
(diethylene triamine pentaacetic acid)
- Patients who cannot undergo MRI
- Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord,
radiological evidence of multifocal disease, or leptomeningeal disease
- Patients who cannot tolerate TMZ
- Severe, active comorbidity, including any of the following:
- Unstable angina and/or congestive heart failure requiring hospitalization
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of study initiation
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy
- Known hepatic insufficiency resulting in clinical jaundice and/or coagulation
defects;
- Known HIV positive status
- 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
toxicity
- Co-medication that may interfere with study results (e.g., immuno-suppressive agents
other than corticosteroids)
- Prior, unrelated malignancy requiring current active treatment with the exception of
cervical carcinoma in situ and adequately treated basal cell or squamous cell
carcinoma of the skin (Treatment with tamoxifen or aromatase inhibitors or other
hormonal therapy that may be indicated in prevention of prior cancer disease
recurrence are not considered current active treatment.)
- Current, recent (within 4 weeks of the administration of this study agent), or planned
participation in an experimental drug study
- Patients are not permitted to have had any other conventional therapeutic intervention
other than steroids prior to enrollment outside of standard of care chemotherapy and
radiation therapy. Patients who receive previous inguinal lymph node dissection,
radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded.
- Known history of autoimmune disease (with the exceptions of medically-controlled
hypothyroidism and Type I Diabetes Mellitus)
