Glioblastoma (GBM) is an aggressive brain cancer. Current therapeutic strategies include
maximal safe surgical resection followed by course of Temozolomide (TMZ) and radiation
therapy (RT). Despite trimodality treatment, recurrence remains inevitable. Our study will
use Daratumumab, an anti-CD38 monoclonal antibody, in combination with TMZ and RT in newly
diagnosed GBM patients. There is pre-clinical evidence suggesting Daratumumab is cytotoxic to
GBM in a multimodal fashion, its safe when combined with chemotherapy & radiation therapy as
well as has the potential to cross blood brain barrier.
Inclusion Criteria:
- Subjects must have high radiological likelihood of GBM with plan for resection/biopsy
for histologically confirmed GBM
- ECOG Performance status ≤ 2
- Subjects must have normal organ and marrow function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin within normal institutional limits
- AST (SGOT) ≤ 3 X institutional upper limit of normal
- ALT (SGPT) ≤ 3 X institutional upper limit of normal
- Serum Creatinine within normal institutional limits OR glomerular filtration rate
(GFR) 60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney
function values, no lower than 30 mL/min/1.73 m2
- The effects of Daratumumab on the developing human fetus are unknown. For this reason,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation.
- Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately.
- Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 4
months after completion of Daratumumab and TMZ administration.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients who received prior treatment for GBM.
- Patients who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Daratumumab and TMZ.
- BCG (Intravesical), Deferiprone, and Dipyrone are risk X category and should be
avoided when Daratumumab is used. Chloramphenicol (Ophthalmic), promazine and
Clozapine are in the risk category C and myelosuppression signs should be monitored
when used in combination with Daratumumab.
- Avoid category Risk X drugs such as BCG (Intravesical), Deferiprone, Dipyrone,
Natalizumab, Tacrolimus (Topical), Vaccines (Live) and Pimecrolimus concurrently with
TMZ. Consider therapy modifications of category D drugs such as Baricitinib,
Echinacea, Fingolimod, Leflunomide, Lenograstim, Lipegfilgrastim, Nivolumab,
Palifermin, Roflumilast, Tofacitinib, Vaccines (Inactivated when used with TMZ.
Monitor therapy for category risk C drugs such as Chloramphenicol (Ophthalmic),
CloZAPine, Coccidioides immitis Skin Test, Denosumab, Ocrelizumab, Pidotimod,
Promazine, Sipuleucel-T, Trastuzumab, and Valproate Products.
- Patients with uncontrolled intercurrent illness.
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements.
- Pregnant women are excluded from this study because there are no animal and human data
to assess the risk of Daratumumab during pregnancy. On the other hand, TMZ is a
category D drug where adverse events are observed in animal reproduction studies. May
cause fetal harm when administered to pregnant females. Male and female patients
should use effective contraception to avoid pregnancy while receiving temozolomide.
May impair male fertility based on animal data).
- Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1
second (FEV1) <50% of predicted normal.
o Note that FEV1 testing is required for participants suspected of having COPD and
participants must be excluded if FEV1 is <50% of predicted normal.
- Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma
of any classification.
o Note that participants who currently have controlled intermittent asthma or
controlled mild persistent asthma are allowed to participate in the study.
- Clinically significant cardiac disease, including:
- Myocardial infarction within 6 months before randomization, or unstable or
uncontrolled disease/condition related to or affecting cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association Class
III-IV).
- Uncontrolled cardiac arrhythmia
