This is an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
B7-H3CART will be administered administered locoregionally (either ICV or both ICV and intratumorally (IT)) at one of the following doses: Dose Level -1: 5 x 10\^6 CAR+ cells (+/- 20%) Dose Level 1: 10 x 10\^6 CAR+ cells (+/- 20%) Dose Level 2: 25 x 10\^6 CAR+ cells (+/- 20%) Dose Level 3: 50 x 10\^6 CAR+ cells (+/- 20%) Dose Level 4: 100 x 10\^6 CAR+ cells (+/- 20%) B7-H3CART Dose Dose Level -1 (DL-1): 5 x 106 B7-H3CART+ cells (± 20%) Dose Level 1 (DL 1): 10 x 106 B7-H3CART+ cells (± 20%) Dose Level 2 (DL2): 25 x 106 B7-H3CART+ cells (± 20%) Dose Level 3 (DL3): 50 x 106 B7-H3CART+ cells (± 20%) Dose Level 4 (DL4): 100 x 106 B7-H3CART+ cells (± 20%) Repeated every 28 days (-7 / +14 days) as long as infusion criteria are met for a total of 6 doses, with an option for an additional 6 doses, up to a total of 12.
Stanford Cancer Institute
Palo Alto, California, United States
RECRUITINGNumber of successful manufacturing product (B7-H3CART) that met minimum assigned dose level range
Defined by the frequency of successful manufacturing runs of B7-H3CART that meet the established IND release criteria for the targeted dose level.
Time frame: 5 years
Maximum Tolerated Dose (MTD) or Recommended phase 2 dose (RP2D)
Defined by the frequency of subjects experiencing dose limiting toxicity (DLT) after initial infusion
Time frame: 5 years
Cumulative Safety of B7-H3CART
At each dose level, incidence and severity of DLT, adverse events and serious adverse events after initial and subsequent infusions of LR B7-H3CART infusion. The definition of DLT in these studies uses NCI's Common Terminology Criteria for Adverse Events (CTCAEv5.0)
Time frame: 5 years
Immunotherapy Response Assessment in Neuro-oncology (iRANO) in subjects with recurrent IDH wild-type GBM
iRano response criteria will be measured by complete response, partial response, minor response, stable disease, progressive disease,
Time frame: 5 years
Time to progression (TTP)
the time from the start (surgical resection) to the date of radiographic progression (death is censored)
Time frame: 5 years
Median overall survival (OS)
time from the date of initial disease diagnosis to the date of death from any cause
Time frame: 5 years
Percentage of subjects able to receive at least three (3) doses of B7-H3CART
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Time frame: 5 years