DC Migration Study for Newly-Diagnosed GBM

• Status: Unknown status
• Trial end date: 2020-08-01
• Target enrollment: 0
• Participant gender: All

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-coinditioning 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gary Archer Ph.D.
• Treatments: Antibodies, Monoclonal; Basiliximab; Dacarbazine; Temozolomide; Vaccines

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)