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


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Trial ID: NCT05474378


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.

Official Title

Phase I Clinical Trial of Locoregionally (LR) Delivered Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Adults With Recurrent Glioblastoma Multiforme (GBM)

Stanford Investigator(s)

Reena Thomas, MD PhD
Reena Thomas, MD PhD

Clinical Associate Professor, Neurology & Neurological Sciences Clinical Associate Professor (By courtesy), Neurosurgery

Gordon Li, MD
Gordon Li, MD

Professor of Neurosurgery and, by courtesy, of Neurology and of Otolaryngology - Head & Neck Surgery (OHNS)

Matthew Frank

Assistant Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Lori Muffly
Lori Muffly

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

David Miklos
David Miklos

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Michael Lim, M.D.
Michael Lim, M.D.

Professor of Neurosurgery and, by courtesy, of Radiation Oncology (Radiation Therapy), of Medicine (Oncology), of Otolaryngology - Head & Neck Surgery (OHNS) and of Neurology

Jasia Mahdi

Clinical Instructor, Neurology


Inclusion Criteria:

   - 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.

   - Use of steroids must be limited to ≤ 4 mg of decadron daily.

   - Adequate organ function at time of screening visit including:

      1. Hgb ≥ 12 g/dL (male) or ≥ 11.5 g/dL (females)

      2. ANC ≥ 1500/uL

      3. Platelets ≥ 100,000/uL

      4. Absolute lymphocyte count ≥150/uL

      5. Serum Creatinine ≤ 1.5mg/dl; Cr clearance should be ≥ 50 mL/min

      6. Serum AST and ALT ≤ 3x ULN (Grade 1)

      7. Total Bilirubin ≤ 1.5 X ULN

      8. PT or PTT ≤ 1.25 X ULN

      9. Cardiac ejection fraction ≥45% without signs of physiologically significant
      pericardial effusion or clinically significant ECG findings.

   10. Baseline oxygen saturation > 92% on room air

   - Subjects of child-bearing or child-fathering potential must be willing to use an
   effective method of contraception (hormonal or two barrier methods) while on study and
   for at least 4 months following the last CAR T cell infusion or as long as B7-H3CART
   are detectable in peripheral blood or CSF.

   - All female subjects of childbearing age must have a negative blood or urine pregnancy

   - Ability to understand and willingness to sign a written informed consent document.

   - Must be willing and able to comply with procedures, return visits and evaluations at
   Stanford Health Care while on this protocol.

   - Prior Therapy:

      - At least 6 weeks following completion of front-line radiation therapy.

      - At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter must
      have elapsed since any prior systemic therapy, except for systemic
      inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.

      - At least 4 weeks from bevacizumab treatment, which can be used only for radiation
      necrosis or pseudo-progression.

      - Prior cytotoxic chemotherapy, radiation, or other anticancer therapies including
      investigational agents discontinued at least 4 weeks prior to Day 1 of treatment.

      - Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except
      for clinically non-significant toxicities such as alopecia).

Exclusion Criteria:

   - 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.

   - Patients receiving anticoagulation therapy.

   - Prior malignancy except previously diagnosed and definitively treated more than 3
   years prior to trial or whose prognosis is deemed good enough to not warrant

   - Clinical evidence of significant increased intracranial pressure (i.e. impending
   herniation) or uncontrolled seizures.

   - Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
   requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial
   pharyngitis are permitted if responding to active treatment.

   - Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C
   virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the
   viral load is undetectable per quantitative PCR and/or nucleic acid testing.

   - Primary immunodeficiency or history of autoimmune disease (e.g. Crohn's, rheumatoid
   arthritis, systemic lupus) resulting in end organ injury or requiring systemic
   immunosuppression/systemic disease modifying agents within the last 2 years.

   - Significant medical diseases or conditions, including poorly controlled conditions:
   i.e. hypertension, cardiovascular disease, diabetes mellitus, chronic obstructive
   pulmonary disease, pulmonary fibrosis, inflammatory disorders, immunodeficiency (e.g.,
   HIV infection), immune compromised for reasons other than malignancy (e.g., chronic
   corticosteroid therapy or other immunosuppressive therapy), renal failure including
   patients requiring dialysis, liver dysfunction, second malignancy (except treated
   basal cell or localized squamous cell skin carcinomas), or active infection.

   - History of bone marrow or stem cell transplantation.

   - In the investigator's judgment, the subject is unlikely to complete all protocol-
   required study visits or procedures, including follow-up visits, or comply with the
   study requirements for participation.


drug: B7-H3CART


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kelly Tanner
(650) 724-5361

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