This randomized phase II trial studies how well cytomegalovirus pp65 peptide-pulsed autologous dendritic cell vaccine (CMV pp65 DC) and diphtheria toxoid/tetanus toxoid vaccine work in treating patients with newly diagnosed glioblastoma. Dendritic cells (DCs) are special “stimulator” cells in the body that can take up proteins released from tumor cells and present pieces of these proteins (called peptides) to create the strong stimulation necessary to activate the immune system. When CMV pp65 DC vaccine is made, it is “pulsed” or loaded with genetic material called RNA (ribonucleic acid), which stimulates the DC to change the RNA into a protein called pp65. This protein is produced by a common virus called cytomegalovirus (CMV). CMV pp65 DC vaccine activates the immune system against the protein so that the immune system may recognize it on the surface of the tumor cells and attack them without harming normal cells. Biological therapies, such basiliximab, use substances made from living organisms that may suppress the immune system in different ways and stop tumor cells from growing. Diphtheria toxoid/tetanus toxoid vaccine (Td) immunization is a drug composed of deactivated (dead) tetanus and diphtheria toxins. Giving the Td prior to vaccine therapy may help CMV pp65 DC vaccine work better by activating the immune response against proteins in the CMV pp65 DC vaccine.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02366728.
PRIMARY OBJECTIVES:
I. To examine the impact of Td pre-conditioning with or without basiliximab on survival.
II. To determine whether pre-conditioning of the vaccine site with Td toxoid systemically increases the migration of CMV pp65 RNA-pulsed DCs to site-draining inguinal lymph nodes.
III. To examine the impact to Td pre-conditioning on survival among patients who are CMV positive.
IV. To assess the impact of Td pre-conditioning on survival among patients who are CMV negative.
SECONDARY OBJECTIVES:
I. To examine the impact of Td pre-conditioning with and without basiliximab on progression-free survival.
II. To examine the impact of Td pre-conditioning at the vaccine site on progression-free survival among patients who are CMV positive.
III. To examine the impact of Td pre-conditioning on progression-free survival among patients who are CMV negative.
EXPLORATORY OBJECTIVES:
I. To describe changes from baseline in immune response as measured by IFN gamma enzyme-linked immunosorbent spot (ELISpot).
II. To assess T cell polyfunctionality when ELISpot results are positive.
III. To describe changes in regulatory T cells (Tregs) over time.
IV. To measure levels of CCL3 and other inflammatory soluble factors.
OUTLINE:
All patients undergo standard of care external beam radiation therapy with concurrent temozolomide for approximately 6 weeks. Patients who have not had a tetanus booster within 5 years receive a standard dose of Td vaccine intramuscularly (IM) the day before the first vaccination. Patients are then randomized to 1 of 3 treatment groups. Patients with progressive disease may be considered for eligibility on the INTERCEPT study (INTracerebral EGFR-vIII Chimeric Antigen Receptor Gene-Modified T Cells for PaTients with Recurrent GBM, Pro00083828).
GROUP I: Beginning 3 weeks after completing concurrent therapy, patients receive maintenance temozolomide orally (PO) on days 1-5. Treatment repeats every 5 weeks for 6-12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive CMV pp65 peptide-pulsed autologous dendritic cell vaccine intradermally (ID) every 2 weeks (vaccinations 1-3) and then every 5 weeks in conjunction with subsequent temozolomide courses (on day 21 of each temozolomide course) for up to 20 total vaccinations in the absence of disease progression. Patients also receive unpulsed dendritic cells one day before the fourth vaccination and indium (In)-111 labeled CMV pp65 peptide-pulsed autologous dendritic cell vaccine ID as the fourth vaccination.
GROUP II: Beginning 3 weeks after completing concurrent therapy, patients receive maintenance temozolomide PO on days 1-5. Treatment repeats every 5 weeks for 6-12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive CMV pp65 peptide-pulsed autologous dendritic cell vaccine ID every 2 weeks (vaccinations 1-3) and then every 5 weeks in conjunction with subsequent temozolomide courses (on day 21 of each temozolomide course) for up to 20 total vaccinations in the absence of disease progression. Patients also receive Td vaccine one day before the fourth vaccination and In-111 labeled CMV pp65 peptide-pulsed autologous dendritic cell vaccine ID as the fourth vaccination.
GROUP III (CLOSED TO ACCRUAL 03/03/2017): Beginning 3 weeks after completing concurrent therapy, patients receive the first 3 DC vaccines every 2 weeks same as Groups I and II. Patients also receive basiliximab intravenously (IV) 7 days before DC vaccine #1 and 7 days before vaccine #2. Prior to the 4th vaccine, patients receive a single dose of Td toxoid administered to the groin on day prior to the fourth DC vaccine.
After completion of study treatment, patients are followed up periodically.
Lead OrganizationDuke University Medical Center
Principal InvestigatorDina Marie Randazzo
