Inclusion Criteria:
- - Histopathologically confirmed recurrent supratentorial WHO grade III or IV malignant
glioma (high grade glioma with molecular features of glioblastoma will be eligible
under WHO grade IV malignant glioma)
- Patient or partner(s) meets one of the following criteria:
1.
Non-childbearing potential (i.e. not sexually active, physiologically incapable
of becoming pregnant, including any female who is post-menopausal or surgically
sterile, or any male who has had a vasectomy). Surgically sterile females are
defined as those with a documented hysterectomy and/or bilateral oophorectomy or
tubal ligation. Postmenopausal for purposes of this study is defined as 1 year
without menses.; or. 2. Childbearing potential and agrees to use one of the following methods of birth
control: approved hormonal contraceptives (e.g. birth control pills, patches,
implants, or infusions), an intrauterine device, or a barrier method of
contraception (e.g. a condom or diaphragm) used with spermicide.
- - Age ≥ 18 years of age at the time of entry into the study.
- - Karnofsky Performance Score (KPS) ≥ 70%
- Hemoglobin ≥ 9 g/dl prior to biopsy.
- - Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study;
however, because of risks of intracranial hemorrhage with catheter placement, platelet
count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter
insertion, which can be attained with the help of platelet transfusion.
- - Neutrophil count ≥ 1000 prior to biopsy.
- - Creatinine ≤ 1.5 x normal range prior to biopsy.
- - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) prior to biopsy (Exception:
Participant has known or 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)
- - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN.
- - Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
Patients
with prior history of thrombosis/embolism are allowed to be on anticoagulation,
understanding that anticoagulation will be held in the perioperative period per the
neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is
preferred. If a patient is on warfarin, the international normalized ratio (INR) is to
be obtained and value should be below 2.0 prior to biopsy.
- - At the time of biopsy, prior to administration of D2C7-IT, the presence of recurrent
tumor must be confirmed by histopathological analysis.
- - A signed informed consent form approved by the Institutional Review Board (IRB) will
be required for patient enrollment into the study.
Patients must be able to read and
understand the informed consent document and must sign the informed consent indicating
that they are aware of the investigational nature of this study.
- - Able to undergo brain MRI with and without contrast.
Exclusion Criteria:
- - Females who are pregnant or breast-feeding.
- - Patients with an impending, life-threatening cerebral herniation syndrome, based on
the assessment of the study neurosurgeons or their designate.
- - Patients with severe, active co-morbidity, defined as follows:
1.
Patients with an active infection requiring intravenous treatment or having an
unexplained febrile illness (Tmax > 99.5°F/37.5°C)
2. Patients with known immunosuppressive disease or known human immunodeficiency
virus infection. 3. Patients with unstable or severe intercurrent medical conditions such as severe
heart disease (New York Heart Association Class 3 or 4)
4. Patients with known lung (forced expiratory volume in the first second of
expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus. 5. Patients with albumin allergy.
- - Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for
nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or
cyclophosphamide (1 week)] prior to starting the study drug unless patients have
recovered from side effects of such therapy.
- - Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study
drug unless patients have recovered from side effects of such therapy.
- - Patients may not have received treatment with tumor treating fields (e.g., Optune) ≤ 1
week prior to starting the study drug.
- - Patients may not be less than 12 weeks from radiation therapy, unless progressive
disease outside of the radiation field or 2 progressive scans at least 4 weeks apart
or histopathologic confirmation.
- - Patients who have not completed all standard of care treatments, including surgical
procedure and radiation therapy (Please note: For patients under 65 years old,
standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks.
For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15v
fractions over 3 weeks.)
1. If the O^6-methylguanine-DNA methyltransferase (MGMT) promoter in their tumor is
known to be unmethylated, patients are not mandated to have received chemotherapy
prior to participating in this trial. 2. If the MGMT promoter in their tumor is known to be methylated or the MGMT
promoter methylation status is unknown at time of screening, patients must have
received at least one chemotherapy regimen prior to participating in this trial.
- - Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord;
radiological evidence of active (growing) disease (active multifocal disease);
extensive subependymal disease (tumor touching subependymal space is allowed); tumor
crossing the midline or leptomeningeal disease.
- - Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the
D2C7-IT infusion.
- - Patients with worsening steroid myopathy (history of gradual progression of bilateral
proximal muscle weakness, and atrophy of proximal muscle groups)
- Patients with 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.
- Patients with active autoimmune disease requiring systemic immunomodulatory treatment
within the past 3 months
