MedulloblastomaPhase 1NCT07087002
GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults
A Phase 1 study testing GPC2-CAR T cells, Fludarabine and Cyclophosphamide in people with Medulloblastoma and Central Nervous System Embryonal Tumor, run by Stanford University at 1 site in United States.
Trial summary
This is a single-site, open-label Phase I treatment study evaluating the manufacturing feasibility and safety of chimeric antigen receptor (CAR) T cells targeting the oncofetal protein Glypican-2 (GPC2) in pediatric and young adult patients with recurrent or refractory (R/R) medulloblastoma. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Medulloblastoma, Central Nervous System Embryonal Tumor, Refractory Medulloblastoma
- What is being tested?
- GPC2-CAR T cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Aug 2025to Aug 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- CNS Embryonal Tumor NOS
- 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.
- 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.
- Evaluable Disease: Evaluable disease as per radiographic findings and/or positive cerebrospinal fluid cytology within 28 days of enrollment.
- 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.
- 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).
- At time of enrollment, subjects are on track to meet the required therapy wash out period(s) prior to apheresis.
- 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)).
- 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.
- At least 28 days following bevacizumab treatment. d. At least 30 days following any investigational drug. e. At least 12 weeks following systemic inhibitory or stimulatory immune checkpoint therapy.
- 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
- 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).
- Normal Organ and Marrow Function [supportive care is allowed per institutional standards, i.e., filgrastim, transfusion]
- Hemoglobin ≥ 8 g/dL
- Absolute Neutrophil Count (ANC) ≥ 1,000/μL
- Platelet count ≥ 75,000/μL, with no platelet transfusion within 96 hours prior to enrollment
- Absolute lymphocyte count (ALC) ≥ 150/μL
- PT/INR, PTT ≤ 1.5 x ULN for age
- Adequate renal, hepatic, cardiac, and pulmonary function defined as:
- Serum creatinine < 1.5 x ULN for age and gender, OR creatinine clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2
- Serum ALT or AST ≤ 3x ULN
- Total bilirubin ≤ 1.5 mg/dL, unless subject has Gilbert's Syndrome
- Cardiac ejection fraction ≥ 45%
- No evidence of physiologically significant pericardial effusion as determined by an ECHO
- No clinically significant ECG findings
- No clinically significant pleural effusion
- Pulse oximetry ≥ 92% on room air, OR forced vital capacity ≥ 50% of predicted value
- Not Pregnant: Females of childbearing potential must have a negative pregnancy test.
- 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.
- 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.
Who cannot join
- Any patient with metastatic disease OUTSIDE the CNS.
- 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.
- Clinical evidence of active/on-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.
- Prior receipt of a chimeric antigen receptor (CAR)-based therapy.
- Currently receiving anticoagulation therapy.
- Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive).
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- 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.
- Pregnancy or breastfeeding in a postpartum female.
- Known sensitivity or allergy to any agents/reagents used in this study.
- 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.
- 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.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Lucile Packard Children's Hospital Stanford
Palo Alto, California, 94304
Mariah Duncan, (650) 497-8953, GPC2CART@stanfordchildrens.org
Katherine Ryan, DO
About this study
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
This is a single-site, open-label Phase I treatment study evaluating the manufacturing feasibility and safety of chimeric antigen receptor (CAR) T cells targeting the oncofetal protein Glypican-2 (GPC2) in pediatric and young adult patients with recurrent or refractory (R/R) medulloblastoma. Subjects with other non-medulloblastoma CNS embryonal tumors may enroll.
- Conditions
- Medulloblastoma, Central Nervous System Embryonal Tumor, Refractory Medulloblastoma, Recurrent Medulloblastoma, Pediatric Brain Tumor, Embryonal Tumor With Multilayered Rosettes (ETMR)
- Being tested
- GPC2-CAR T cells, Fludarabine, Cyclophosphamide
- Keywords
- 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
- Medical subject headings
- Medulloblastoma, Neuroectodermal Tumors, Primitive, Pinealoma, Rhabdoid Tumor, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GPC2-CAR T cellsGenetic
Also called GPC2-directed CAR T cells
Autologous T cells transduced with a retroviral vector encoding a second-generation GPC2-targeted chimeric antigen receptor (GPC2-CAR), administered intracerebroventricularly. Up to 16 doses (cycles) are administered using an intrapatient dose-escalation strategy. Cycle 2 may occur no earlier than Day 28 following Cycle 1, and Cycles 3 through 16 may occur as early as Day 22 following the preceding cycle.
FludarabineDrug
Participants who meet eligibility criteria for lymphodepletion chemotherapy will receive fludarabine 30 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing <12 kg will receive protocol-specified dose adjustments.
CyclophosphamideDrug
Participants who meet eligibility criteria for lymphodepletion chemotherapy will receive cyclophosphamide 500 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing <12 kg will receive protocol-specified dose adjustments.
| Study group | Role | What they receive |
|---|---|---|
| GPC2-CAR T Cell Therapy | Experimental | Participants will undergo leukapheresis for collection of peripheral blood mononuclear cells, which will be used to manufacture autologous T cells transduced with a retroviral vector encoding a GPC2-targeted chimeric antigen receptor (GPC2-CAR T cells). After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, participants will receive up to 16 cycles of intracerebroventricular (ICV) GPC2-CAR T cell infusions using an intrapatient dose escalation strategy. Receives: Genetic: GPC2-CAR T cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Manufacturing Feasibility
Proportion of manufacturing attempts that result in at least one dose of GPC2-CAR T cells that meet the IND release criteria and protocol-specified dose.
Measured: Up to 6 months post-leukapheresis
Incidence of Dose Limiting Toxicities (DLTs)
Number and severity of DLTs following GPC2-CAR T cell administration at each dose level using protocol-defined criteria.
Measured: Within first 28-day treatment cycle per dose level
Secondary outcomes (3)
Objective Response Rate (ORR)
Percentage of subjects achieving a protocol-defined response (complete response, partial response, or stable disease) based on imaging and neurological exam.
Measured: Up to 2 years post-infusion
Progression-Free Survival (PFS)
Time from enrollment to radiographic disease progression.
Measured: Up to 2 years
Overall Survival (OS)
Time from initial diagnosis to death from any cause.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2025
- Study start28 Aug 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MedulloblastomaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katherine Ryan, DO, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07087002
- Sponsor's protocol ID
- IRB-79066
- Other IDs
- NCI-2025-06836
- Status last verified
- Oct 2026
- First submitted
- 24 Jun 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07087002
- Acronym / sponsor ID
- IRB-79066
- Conditions
- Medulloblastoma, Central Nervous System Embryonal Tumor, Refractory Medulloblastoma, Recurrent Medulloblastoma, Pediatric Brain Tumor, Embryonal Tumor With Multilayered Rosettes (ETMR)
- Keywords
- GPC2-CAR T cells, Chimeric Antigen Receptor T cells, Intracerebroventricular CAR T, Pediatric CNS tumors, Immunotherapy, Medulloblastoma, Refractory brain tumors, T cell therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 28 Aug 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 25 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-site, open-label Phase I treatment study evaluating the manufacturing feasibility and safety of chimeric antigen receptor (CAR) T cells targeting the oncofetal protein Glypican-2 (GPC2) in pediatric and young adult patients with recurrent or refractory (R/R) medulloblastoma. Subjects with other non-medulloblastoma CNS embryonal tumors may enroll.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GPC2-CAR T Cell Therapy | Experimental | Genetic: GPC2-CAR T cells, Drug: Fludarabine, Drug: CyclophosphamideParticipants will undergo leukapheresis for collection of peripheral blood mononuclear cells, which will be used to manufacture autologous T cells transduced with a retroviral vector encoding a GPC2-targeted chimeric antigen receptor (GPC2-CAR T cells). After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, participants will receive up to 16 cycles of intracerebroventricular (ICV) GPC2-CAR T cell infusions using an intrapatient dose escalation strategy. |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (36 listed)
- Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)
- 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.
- 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.
- Evaluable Disease: Evaluable disease as per radiographic findings and/or positive cerebrospinal fluid cytology within 28 days of enrollment.
- 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.
Key exclusion criteria (14 listed)
- Any patient with metastatic disease OUTSIDE the CNS.
- 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.
- Clinical evidence of active/on-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.
- Prior receipt of a chimeric antigen receptor (CAR)-based therapy.
- Currently receiving anticoagulation therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GPC2-CAR T cellsAlso: GPC2-directed CAR T cellsAutologous T cells transduced with a retroviral vector encoding a second-generation GPC2-targeted chimeric antigen receptor (GPC2-CAR), administered intracerebroventricularly. Up to 16 doses (cycles) are administered using an intrapatient dose-escalation strategy. Cycle 2 may occur no earlier than Day 28 following Cycle 1, and Cycles 3 through 16 may occur as early as Day 22 following the preceding cycle. | Genetic | GPC2-CAR T Cell Therapy |
| FludarabineParticipants who meet eligibility criteria for lymphodepletion chemotherapy will receive fludarabine 30 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing <12 kg will receive protocol-specified dose adjustments. | Drug | GPC2-CAR T Cell Therapy |
| CyclophosphamideParticipants who meet eligibility criteria for lymphodepletion chemotherapy will receive cyclophosphamide 500 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing <12 kg will receive protocol-specified dose adjustments. | Drug | GPC2-CAR T Cell Therapy |
Primary outcome
Manufacturing Feasibility
Time frame: Up to 6 months post-leukapheresis
Proportion of manufacturing attempts that result in at least one dose of GPC2-CAR T cells that meet the IND release criteria and protocol-specified dose.
Incidence of Dose Limiting Toxicities (DLTs)
Time frame: Within first 28-day treatment cycle per dose level
Number and severity of DLTs following GPC2-CAR T cell administration at each dose level using protocol-defined criteria.
3 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 2 years post-infusion
Progression-Free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Katherine Ryan, DO principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GPC2-CAR T cells, Fludarabine and Cyclophosphamide in people with Medulloblastoma and Central Nervous System Embryonal Tumor, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mariah Duncan ((650) 497-8953, GPC2CART@stanfordchildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Manufacturing Feasibility (time frame: Up to 6 months post-leukapheresis). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.