DC Migration Study to Evaluate TReg Depletion In GBM Patients With and Without Varlilumab (DERIVe)

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Dendritic cells, Temozolomide, Duke University, Varlilumab, Desjardins Read More

Inclusion Criteria:

• Age ≥18 years of age.
• Glioblastoma with definitive resection prior to enrollment, with residual radiographic contrast enhancing disease on the post-operative CT or MRI of <1 cm in maximal diameter in any plane.
• Able to receive SOC RT/TMZ for approximately 6 weeks duration and of more than 54GY
• MRI post RT does not show progressive disease outside the radiation field
• Enough tumor tissue available for determination of MGMT gene promoter status.
• CMV Seropositive
• KPS of ≥ 70%
• Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl.
• Serum creatinine ≤3 times institutional upper limit of normal for age, serum SGOT ≤ 3 times institutional upper limit of normal f.or age and bilirubin ≤ 1.5 times upper limit of normal prior to starting TMZ cycle 1 (Exception to bilirubin criteria: 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 x ULN is acceptable).
• Signed informed consent approved by the Institutional Review Board.
• 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.
• Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates).
• Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease.

• 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 and Hepatitis C 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.)
• 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.
• Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study.
• Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus).