GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults

Launched by STANFORD UNIVERSITY · Jul 17, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment called GPC2-CAR T cell therapy for children and young adults who have a type of brain tumor called medulloblastoma or similar tumors that have come back or have not responded to previous treatments. This therapy uses the patient’s own immune cells, which are specially modified in the lab to target and attack the tumor cells. These modified cells are then given directly into the fluid around the brain through a small device, with the goal of finding out if this approach is safe and shows early signs of helping patients.

To be part of the study, patients need to be between 1 year and 30 years old, have a confirmed diagnosis of medulloblastoma or related brain tumors, and have tumors that test positive for a specific protein called GPC2. The tumor must have come back or not improved after standard treatments. Patients also need to be well enough to handle the treatment and have certain normal blood and organ functions. If eligible, participants will receive the modified immune cells through a small device placed in the brain fluid, and doctors will closely monitor their safety and how well the treatment works. It’s important to know that this is an early-phase trial focused mainly on safety and feasibility, and the treatment is still being studied to learn more about its effects.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)
• * Other acceptable CNS embryonal tumors include:
• • Embryonal Tumor with Multilayered Rosettes (ETMR)
• • Pineoblastoma
• • Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS
• • CNS neuroblastoma, FOXR2-activated
• • CNS Embryonal Tumor NOS
• • 2. Recurrent/Refractory Disease: History of relapsed and/or recurrent disease defined as tumor progression or recurrence following initial diagnosis and upfront treatment with curative intent, or failure to achieve disease control with standard curative-intent therapy.
• • 3. GPC2 Positive: H-score ≥ 100 by IHC staining performed on the (Prescreening Protocol IRB-78780, PI: Katherine Ryan, DO) at Stanford Clinical Anatomic Pathology Lab for GPC2 from a tumor sample any time since initial diagnosis.
• • 4. Evaluable Disease: Evaluable disease as per radiographic findings and/or positive cerebrospinal fluid cytology within 28 days of enrollment.
• • 5. Patients with VP shunts: Patients with pre-existing ventriculo-peritoneal (VP) shunt devices must have a programmable shunt device to enroll on this study. A VP shunt is not a requirement for this study.
• • 6. Prior therapy: No limit to the number of prior treatment regimens. Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia, nutritional support measures, electrolyte abnormalities, or those not impacting the investigator's ability to assess treatment emergent toxicities).
• The following wash-out periods apply at time of enrollment:
• • a. At least 6 weeks following craniospinal radiation therapy. i. At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).
• • b. At least 21 days 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.
• • c. At least 28 days following bevacizumab treatment. d. At least 30 days following any investigational drug.
• • 7. Age: ≥ 12 months to ≤ 30 years of age at time of enrollment The first 3 subjects treated with GPC2-CAR T cells must be ≥ 3 years old at time of infusion
• • 8. Performance Status: Subjects ≥ 16 years of age must have Karnofsky ≥ 60%. Subjects \< 16 years of age must have Lansky scale 60%; or ECOG performance status ≤ 2 (see Section 11.3).
• • 9. Normal Organ and Marrow Function \[supportive care is allowed per institutional standards, i.e., filgrastim, transfusion\]
• • 1. Hemoglobin ≥ 8 g/dL
• • 2. Absolute Neutrophil Count (ANC) ≥ 1,000/μL
• • 3. Platelet count ≥ 75,000/μL, with no platelet transfusion within 96 hours prior to enrollment
• • 4. Absolute lymphocyte count (ALC) ≥ 150/μL
• • 5. PT/INR, PTT ≤ 1.5 x ULN for age
• Adequate renal, hepatic, cardiac, and pulmonary function defined as:
• • 6. Serum creatinine \< 1.5 x ULN for age and gender, OR creatinine clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2
• • 7. Serum ALT or AST ≤ 3x ULN
• • 8. Total bilirubin ≤ 1.5 mg/dL, unless subject has Gilbert's Syndrome
• • 9. Cardiac ejection fraction ≥ 45%
• • 10. No evidence of physiologically significant pericardial effusion as determined by an ECHO
• • 11. No clinically significant ECG findings
• • 12. No clinically significant pleural effusion
• • 13. Pulse oximetry ≥ 92% on room air, OR forced vital capacity ≥ 50% of predicted value
• • 10. Not Pregnant: Females of childbearing potential must have a negative pregnancy test.
• • 11. Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen or for as long as CAR T cells are detectable in peripheral blood.
• • 12. Must provide informed consent. All subjects ≥ 18 years of age must be able to give informed consent. For subjects \<18 years old or adults with limited decision-making capacity, their legal authorized representative (LAR) (i.e., parent or guardian) must give informed consent. Pediatric subjects will be included in age-appropriate discussion and assent will be obtained for those \> 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he/she will be asked to reconsent as an adult.
• • Exclusion Criteria
• • 1. Any patient with metastatic disease OUTSIDE the CNS.
• • 2. Unwilling or unable, in the investigator's judgement, to have a CSF reservoir (Ommaya or Rickham) placed. Does not apply to subjects who have a pre-existing device suitable for ICV delivery of CAR T cells and ICP monitoring.
• • 3. Clinical evidence of active/on-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.
• • 4. Prior receipt of a chimeric antigen receptor (CAR)-based therapy.
• • 5. Currently receiving anticoagulation therapy.
• • 6. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive).
• • EXCEPTION: A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• • 7. Pregnancy or breastfeeding in a postpartum female.
• • 8. Known sensitivity or allergy to any agents/reagents used in this study.
• • 9. History of prior other malignancy. EXCEPTION: Previously diagnosed and definitively treated more than 5 years prior to enrollment or whose prognosis is deemed good enough to not warrant surveillance.
• • 10. 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.
• • 11. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• • 12. Significant medical diseases or poorly controlled conditions that, in the judgement of the investigator, put the subject at an unacceptable risk of complications, including but not limited to: uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, pulmonary fibrosis, clinically significant inflammatory disorders, immunodeficiency (e.g., HIV infection), immunocompromised for reasons other than malignancy (e.g., chronic corticosteroid therapy or other immunosuppressive therapy), renal failure including patients requiring dialysis, or clinically significant liver dysfunction.
• • 13. In the Investigator's judgment, the subject or parents/caregivers (as required) will not be able to comply with the study procedures outlined in the study protocol including follow-up visits.