RECRUITING

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

Conditions

Medulloblastoma Central Nervous System Embryonal Tumor Refractory Medulloblastoma Recurrent Medulloblastoma Pediatric Brain Tumor Embryonal Tumor With Multilayered Rosettes (ETMR)Pineoblastoma Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS CNS Neuroblastoma FOXR2-activated GPC2-CAR T cells Chimeric Antigen Receptor T cells Intracerebroventricular CAR T Pediatric CNS tumors Immunotherapy Refractory brain tumors T cell therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single-site, open-label Phase 1 clinical trial evaluating the feasibility, safety, and preliminary activity of autologous GPC2-targeted chimeric antigen receptor (CAR) T cells administered via intracerebroventricular (ICV) infusion in children and young adults with relapsed or refractory medulloblastoma or other eligible Central Nervous System (CNS) embryonal tumors.

Official Title

Phase I Clinical Trial of GPC2 Chimeric Antigen Receptor T (GPC2-CAR T) Cells for Relapsed or Refractory Medulloblastoma in Children and Young Adults

Quick Facts

Study Start:2025-08-25

Study Completion:2027-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07087002

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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). 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 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. 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). 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.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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).
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
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.
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).
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.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Mariah Duncan

CONTACT

(650) 497-8953

GPC2CART@stanfordchildrens.org

Principal Investigator

Katherine Ryan, DO

PRINCIPAL_INVESTIGATOR

Stanford University

Study Locations (Sites)

Lucile Packard Children's Hospital Stanford

Palo Alto, California, 94304

United States

Collaborators and Investigators

Sponsor: Stanford University

Katherine Ryan, DO, PRINCIPAL_INVESTIGATOR, Stanford University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-25

Study Completion Date2027-08

Study Record Updates

Study Start Date2025-08-25

Study Completion Date2027-08

Terms related to this study

Keywords Provided by Researchers

GPC2-CAR T cells
Chimeric Antigen Receptor T cells
Intracerebroventricular CAR T
Pediatric CNS tumors
Immunotherapy
Medulloblastoma
Refractory brain tumors
T cell therapy
Embryonal Tumor with Multilayered Rosettes (ETMR)
Pineoblastoma
Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS
CNS neuroblastoma
FOXR2-activated

Additional Relevant MeSH Terms

Medulloblastoma
Central Nervous System Embryonal Tumor
Refractory Medulloblastoma
Recurrent Medulloblastoma
Pediatric Brain Tumor
Embryonal Tumor With Multilayered Rosettes (ETMR)
Pineoblastoma
Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS
CNS Neuroblastoma
FOXR2-activated