Inclusion Criteria:
* Patients must have a recurrent supratentorial WHO grade III or IV malignant glioma based on imaging studies;
* Prior histopathology consistent with a supratentorial WHO grade III or IV malignant glioma;
* Following biopsy, prior to administration of D2C7-IT, the presence of recurrent tumor must be confirmed by histopathological analysis;
* Age ≥ 18 years of age;
* Karnofsky Performance Status (KPS) ≥ 70%;
* Laboratory Values:
* 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;
* Hemoglobin ≥ 9 gm/dL prior to biopsy;
* Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 prior to biopsy;
* Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) prior to biopsy;
* Liver Function: Total bilirubin ≤ 1.5 x ULN prior to biopsy (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.); AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 2.5 x the ULN prior to biopsy;
* Prothrombin (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x upper limit of normal (ULN) prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anti-coagulation will be held in the peri-operative 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;
* Ability to comply with study and follow-up procedures;
* If the patient is a sexually active female of child bearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of child bearing potential, the patient must agree to use appropriate contraceptive measures for the duration of the treatment of the tumor and for 6 months afterwards as stated in the informed consent. Female patients of child bearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the D2C7-IT infusion
* Patients will sign an IRB-approved informed consent form prior to any study-related procedures.
* Able to undergo brain MRI with and without contrast.
Exclusion Criteria:
* 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;
* Pregnant or breastfeeding;
* Patients with contrast-enhancing tumor component crossing the midline, actively growing multi-focal tumor, infratentorial tumor or extensive tumor dissemination (subependymal or leptomeningeal);
* Patients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment;
* Patients with a known severe allergy to Gadolinium-DTPA. Patients with mild allergies (e.g., rash only) will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent;
* Unstable systemic disease in the opinion of the treating physician, for example active infection requiring IV antibiotics;
* Patients on greater than 4mg per day of dexamethasone within the 2 weeks prior to admission for D2C7-IT infusion;
* Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups);
* Patients who have not completed standard of care treatment prior to participation in this trial, i.e. surgical procedure and radiation therapy (at least 59 Gy). Note: If tumor is unmethylated, patients are not mandated to have received chemotherapy prior to participation in this trial. However, if tumor is methylated, patients must have received at least one chemotherapy regimen prior to participation in this trial.
* 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;
* Treated with immunotherapeutic agents within 4 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy;
* Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy;
* Treated with alkylating agents within 4 weeks before enrollment (6 weeks for nitrosoureas) or treated within 1 week before enrollment with daily or metronomic chemotherapy, unless the patient has recovered from the expected toxic effects of such therapy;
* Prior chemotherapy (non-alkylating agents) within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy.
