Trial Outcomes & Findings for EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma (NCT NCT02664363)

Last Updated: 2023-02-17

Results Overview

Within this "3+3" phase I study, the primary objective is to determine the MTD of a single IV infusion of EGFRvIII CAR T cells in patients with newly-diagnosed WHO grade IV malignant glioma. Four dose levels were to be considered based on transduced cells/kg: #1: 4.5 x 10\^6/kg, #2: 1.5 x 10\^7/kg, #3: 4.5 x 10\^7/kg, and #4: 1.5 x 10\^8/kg. The MTD is the highest dose level at which ≤1 of 3-6 patients experience dose-limiting toxicity during the 4 weeks after CAR infusion.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

12-18 months

Results posted on

2023-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	EGFRvIII CAR T Cells 4.5 x 10\^6 EGFRvIII CAR T Cells/kg - Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EGFRvIII CAR T Cells n=3 Participants 4.5 x 10\^6 EGFRvIII CAR T Cells/kg: Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Age, Continuous	58.33 years STANDARD_DEVIATION 3.79 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12-18 months

Population: All patients who received EGFRvIII CAR T cells

Outcome measures

Outcome measures
Measure	EGFRvIII CAR T Cells n=3 Participants 4.5 x 10\^6 EGFRvIII CAR T cells/kg: Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Maximally Tolerated Dose	NA Cells/kg The study terminated before a MTD could be determined.

SECONDARY outcome

Timeframe: 12-18 months

Population: All patients who received EGFRvIII CAR T cells

DLT is defined as any Grade IV event of any duration that is at least (possibly, probably, or definitely) attributable to EGFRvIII CARs, or any Grade III toxicity that is at least (possibly, probably, or definitely) attributable to EGFRvIII CARs that is not reversible within 4 weeks.

Outcome measures

Outcome measures
Measure	EGFRvIII CAR T Cells n=3 Participants 4.5 x 10\^6 EGFRvIII CAR T cells/kg: Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Number of Patients Who Experienced a Dose-limiting Toxicity (DLT)	0 Participants

Adverse Events

EGFRvIII CAR T Cells

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	EGFRvIII CAR T Cells n=3 participants at risk 4.5 x 10\^6 EGFRvIII CAR T cells/kg: Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 1/3 • 1 year
Psychiatric disorders Confusion	33.3% 1/3 • 1 year

Other adverse events

Other adverse events
Measure	EGFRvIII CAR T Cells n=3 participants at risk 4.5 x 10\^6 EGFRvIII CAR T cells/kg: Autologous T cells transduced with a retroviral vector encoding for a chimeric antigen receptor (CAR) directed against the tumor specific antigen, EGFRvIII
Blood and lymphatic system disorders Anemia	33.3% 1/3 • 1 year
Eye disorders Eye disorders - Other, Specify: DOUBLE VISION, INTERMITTENT	33.3% 1/3 • 1 year
Eye disorders Vitreous hemorrhage	33.3% 1/3 • 1 year
Gastrointestinal disorders Nausea	33.3% 1/3 • 1 year
Gastrointestinal disorders Vomiting	33.3% 1/3 • 1 year
General disorders Edema limbs	33.3% 1/3 • 1 year
General disorders Gait disturbance	66.7% 2/3 • 1 year
Infections and infestations Infections and infestations - Other, Specify: FUNGUS FEET AND GROIN	33.3% 1/3 • 1 year
Infections and infestations Infections and infestations - Other, Specify: RING WORM	33.3% 1/3 • 1 year
Investigations Lymphocyte count decreased	33.3% 1/3 • 1 year
Investigations Platelet count decreased	33.3% 1/3 • 1 year
Investigations White blood cell decreased	33.3% 1/3 • 1 year
Metabolism and nutrition disorders Hyperglycemia	33.3% 1/3 • 1 year
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • 1 year
Nervous system disorders Cognitive disturbance	33.3% 1/3 • 1 year
Nervous system disorders Dizziness	33.3% 1/3 • 1 year
Nervous system disorders Dysphasia	33.3% 1/3 • 1 year
Psychiatric disorders Insomnia	33.3% 1/3 • 1 year
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Specify: FLUSHED/REDNESS	33.3% 1/3 • 1 year
Vascular disorders Hypertension	100.0% 3/3 • 1 year

Additional Information

Principal Investigator

Duke University Medical Center

Phone: 9196845301

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place