DC Migration Study for Newly-Diagnosed GBM
Condition: Glioblastoma; Astrocytoma, Grade IV; Giant Cell Glioblastoma; Glioblastoma Multiforme
MeSH terms: Glioblastoma; Astrocytoma
Intervention: Unpulsed DCs; Td; Human CMV pp65-LAMP mRNA-pulsed autologous DCs; 111In-labeled DCs; Temozolomide; Saline; Basiliximab
Intervention description: Patients in Group I will receive 1 x 10^6 autologous unpulsed DCs in saline administered to a single side of the groin intradermally 1 day before the fourth vaccine.; Patients in Groups II and III will receive a single dose of Td toxoid (1 flocculation unit, Lf, in 0.4 mLs) administered to a single side of the groin given intradermally 1 day before the fourth vaccine.; 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.; 111In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs will be labeled with 111In (50 μCi / 5 x 10^7 DCs) and given i.d. as fourth vaccine for Groups I and II only.; Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 5 (± 1) weeks for a total of 6 to 12 cycles at the discretion of the treating oncologist.; 0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups; Group III will receive basiliximab infusions (20 mg I.V) 1 week before the first vaccine and 1 week before the second vaccine.
Intervention MeSH terms: Temozolomide; Basiliximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This randomized phase II study will assess the impact of pre-conditioning on migration and
      survival among newly diagnosed glioblastoma (GBM) patients who have undergone definitive
      resection and completed standard temozolomide (TMZ) and radiation treatment, as well as the
      impact of tetanus pre-conditioning and basiliximab together on survival. After completing
      standard of care radiotherapy with concurrent TMZ, patients will be randomized to 1 of 3
      treatment arms: 1). receive cytomegalovirus (CMV)-specific dendritic cell (DC) vaccines with
      unpulsed (not loaded) DC pre-conditioning prior to the 4th vaccine; 2). receive CMV-specific
      DC vaccines with Tetanus-Diphtheria Toxoid (Td) pre-conditioning prior to the 4th vaccine;
      3). receive basiliximab infusions prior to the 1st and 2nd DC vaccines along with Td
      pre-conditioning prior to the 4th vaccine. A permuted block randomization algorithm using a
      1:1:1 allocation ratio will be used to assign patients to a treatment arm. Randomization will
      be stratified by CMV status (positive, negative), with the assignment to arms I and II being
      double-blinded. Effective March 2017, randomization to Group III has been terminated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years of age

          -  WHO Grade IV Glioma with definitive resection prior to enrollment, with residual
             radiographic contrast enhancing disease on the post-operative CT or Magnetic Resonance
             Imaging (MRI) of <1 cm in maximal diameter in any axial plane

          -  MRI post radiation therapy (RT) does not show progressive disease at time of
             randomization

          -  Karnofsky Performance Status of > 80%.

          -  Hemoglobin ≥ 9.0 g/dl, Absolute Neutrophil Count ≥ 1,500 cells/µl, platelets ≥ 125,000
             cells/µl

          -  Serum creatinine ≤ 1.5 mg/dl, Serum Glutamic Oxaloacetic Transaminase & bilirubin ≤
             1.5 times upper limit of normal

          -  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 [IUDs; only hormonal], sexual
             abstinence or vasectomized partner) during the trial & 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 negative serum pregnancy
             test within 48 hours prior to first study procedure (leukapheresis).

          -  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 & for a period of >
             6 months following the last administration of trial drugs

        Exclusion Criteria:

          -  Pregnant or breast-feeding

          -  Women of childbearing potential & 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-Diethylenetriaminepentaacetic Acid

          -  Patients who cannot undergo MRI or SPECT 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 Human Immunodeficiency Virus 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;

          -  Patients are not permitted to have had any other conventional therapeutic intervention
             other than steroids prior to enrollment outside of standard of care chemotherapy &
             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)