Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorHideho Okada, MD, PhD
About this trial
This phase I trial tests the safety, side effects, and best dose of E-SYNC chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy in treating patients with EGFRvIII positive (+) glioblastoma. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so the CAR T cells will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine before treatment with CAR T cells may make the CAR T cells more effective.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age >= 18 years.
Karnofsky performance status (KPS) score of >=70.
Peripheral absolute neutrophil count >=1000/mm^3.
Platelet count >=100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
Disqualifiers
Exclusion Criteria for Cohort 1
Participant who has been treated with any investigational agents and chemotherapy targeting GBM <= 4 weeks prior to date of study registration. Exceptions to this include: must be >=23 days from last dose of temozolomide (TMZ) or radiotherapy, mush be >= 6 weeks from last dose of nitrosourea.
Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of eligibility confirmation.
Known addiction to alcohol or illicit drugs.
Trial design
Design model
Sequential
Treatments tested in this trial
E-SYNC T Cells
Biological/VaccineGiven IV
Cyclophosphamide (non-investigational)
DrugGiven IV
Fludarabine (non-investigational)
DrugGiven IV
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Surgical resection
Procedure/SurgeryUndergo surgical resection of tumor tissue
Treatment groups
20 Participants
are divided into 3 treatment groupsGroup A: Cohort 1: Starting Dose Level 1 (5 x 10^7 CAR+ cells) (DL1)Experimental treatment 0 interventions
Group B: Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2)Experimental treatment 4 interventions
Group C: Cohort 2: Tissue analysis cohortExperimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Proportion of participants reporting treatment-emergent adverse events
Treatment-emergent adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Time frame
Up to 96 weeksSecondary outcomes
1
Percentage of participants who successfully receive E-SYNC T cells
The percentage of participants for whom a sufficient quantity of drug product (E-SYNC T cells) could be manufactured from peripheral blood mononuclear cells (PBMC) obtained at apheresis and administered will be reported.
Time frame
Up to 96 weeks2
The percentage of primed E-SYNC T (Cohort 2 only) cells in TIL versus PBMC will be evaluated
The percentage of primed E-SYNC T cells in tumor-infiltrating lymphocytes (TIL) versus Peripheral blood mononuclear cell (PBMC) will be evaluated using single-cell RNA sequencing as a pilot study and described in 5 participants.
Time frame
Up to 96 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Hideho Okada, MD, PhD
Lead sponsor
University of California, San Francisco
Sponsor institution
California Institute for Regenerative Medicine (CIRM)
Collaborator
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov