The objectives of this phase I first-in-human trial are to evaluate safety, feasibility, and preliminary efficacy of an individualized Bvax vaccine in addition to standard of care chemoradiation in patients with newly diagnosed glioblastoma.
Patients will be enrolled following surgery or biopsy, confirming the diagnosis of glioblastoma. Leukapheresis may start any time after enrollment and before the start of adjuvant temozolomide (TMZ), ideally prior to starting radiation therapy (RT) with concomitant TMZ chemoradiation. Bvax vaccine production will occur during chemoradiation (TMZ/RT). Patients will first undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMC) to produce Bvax. The CD19+ B cells will then be enriched for 4-1BBL+ cells that will be expanded in a cell culture and primed with tumor lysate from the patient's tissue. After passing quality control, the Bvax product will be cryopreserved at - 135oC. During the same process the CD8 T cells will be cryopreserved without further manipulation or expansion. Vaccine administration consisting of Bvax and autologous T cells will occur weekly, for a total of 4 doses. After completion of Bvax, patients may resume standard of care (SOC) with adjuvant TMZ with or without Tumor Treating Fields (TTFields), as clinically indicated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
The study treatment includes dose-escalation of B-cell vaccine (Bvax) and a fixed dose of autologous CD8 T cells reinfusion integrated in the standard of care therapy for glioblastoma. Bvax is a biological product that is produced for each patient individually from the cells collected through leukapheresis. The Bvax treatment will be administrated once a week for a total of 4 doses. The following dose levels (DL) will be explored: * DL1: 0.5 x 106 Bvax/kg/injection and 2 x 106/kg/injection. * DL 2: 1.0 x 106 Bvax/kg/injection and T cells 2 x 106/kg/injection
Northwestern University
Chicago, Illinois, United States
Incidence of adverse events
Safety will be assessed by evaluating the incidence of adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0.
Time frame: Up to 90 days after the first dose of Bvax and/or T-cell
Progression-free survival (PFS) rate
Defined as the proportion of patients who remain alive and progression-free at six, twelve, and eighteen months from treatment initiation.
Time frame: Up to five years
Overall survival (OS) rate
Overall survival (OS) is defined as the length of time the participant is alive after the start of treatment.
Time frame: Up to five years
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