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B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Recurrent Glioblastoma Multiforme

ConditionBrain and Nervous System
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorStanford University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically confirmed high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features, tested as IDH wild-type, as per revised WHO 2021 criteria. Patients must also have evidence of tumor recurrence/progression by MRI (RANO criteria) after standard front-line therapy. b. First recurrence or progressive disease after a standard line therapy.

Resectable disease: Resection is being considered as part of the standard of care for the patient and it is thought that it is feasible that a majority of contrast-enhancing tumor mass/signal can be resected.

Patients must be between the ages of 18 and 75 years old (inclusive).

Karnofsky Performance score ≥ 60.

Disqualifiers

Pregnant or patients who are breastfeeding.

Prior or concurrent treatment with Avastin (bevacizumab) for the purposes of recurrent disease. Avastin (bevacizumab) may have been used for radiation necrosis.

Prior exposure to chimeric antigen receptor (CAR) based therapies.

Known sensitivity or allergy to any agents/reagents used in this study.

Trial design

Design model

Sequential

Treatments tested in this trial

  • B7-H3CART

    Drug

    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.

Treatment groups

39 Participants
are divided into 2 treatment groups
Group A: Dose escalationExperimental treatment 1 intervention
Group B: Dose ExpansionExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Number 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
2

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

Secondary outcomes

1

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
2

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
3

Time to progression (TTP)

the time from the start (surgical resection) to the date of radiographic progression (death is censored)

Time frame
5 years
4

Median overall survival (OS)

time from the date of initial disease diagnosis to the date of death from any cause

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

California Institute for Regenerative Medicine (CIRM)

Collaborator

Parker Institute for Cancer Immunotherapy

Collaborator

Source ClinicalTrials.gov
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