ClinicalTrials.gov record NCT04196413
GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas (DIPG) & Spinal Diffuse Midline Glioma(DMG)
Phase 1 Clinical Trial of Autologous GD2 Chimeric Antigen Receptor (CAR) T Cells (GD2CART) for H3K27M-mutant Diffuse Midline Glioma (DMG)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Phase 1 trial of autologous GD2 CAR T cells for people with H3K27M‑mutant diffuse midline glioma, including DIPG and spinal DMG. The study will test whether the CAR T cells can be manufactured and safely given, using intravenous or intracerebroventricular delivery; some groups receive preparative chemotherapy. It uses dose-escalation and expansion cohorts to evaluate dosing, route, and short-term safety.
What it is studying. This study is testing autologous T cells engineered to express a GD2 chimeric antigen receptor (GD2CART) in people with H3K27M‑mutant diffuse midline glioma. Main aims are to determine whether GD2CART can be manufactured using a specified retroviral process, to assess safety and find a maximum tolerated dose or recommended phase 2 dose (including choice of route and schedule), and to study repeat intracerebroventricular dosing and the ability of a dimerizing agent (AP1903) to clear the engineered cells if serious toxicity occurs.
What the researchers hope to learn. Scientific goals: determine feasibility of manufacturing GD2CART with the specified retroviral method; identify safety, dose, route and schedule (MTD/RP2D) of GD2CART and preparative chemotherapy; evaluate safety and effects of repeat intracerebroventricular administrations; assess whether AP1903 can clear the engineered cells if needed; and collect preliminary measures of radiographic response, overall survival, progression‑free survival, and patient‑reported outcomes.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The primary purpose of this study is to test whether CAR T cells targeting GD2 (GD2CART) can be successfully made and safely given to children and adults with H3K27M-mutant diffuse midline glioma (DMG). Eligible subjects may have DMG arising in the pons (called difuse intrinisic pontine glioma, DIPG), the spinal cord, or other areas of the brain such as a thalamus
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- GD2 CAR T cells
- Fludarabine
- Cyclophosphamide
- Rituximab
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Disease Status: Diagnosis of H3K27M mutant diffuse midline glioma (DMG)
- H3K27M or H3K27I mutation. Confirmed by CLIA test.
- Age: Greater than or equal to 2 year of age and less than or equal to 60 years of age.
- Prior Therapy:
- At least 4 weeks following completion of standard upfront 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 that requires 3 months.
- Dordaviprone (Modeyso), previously known as ONC201, may be taken as prior therapy but - just as with other anti-cancer medications - administration must cease at least 5 half-lives prior to enrollment
- Performance Status:
- Subjects > 16 years of age: Karnofsky ≥ 60% OR Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Subjects ≤ 16 years of age: Lansky scale ≥ 60%.
- Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion) i. ANC ≥ 1000/uL ii. Platelet count ≥ 100,000/uL iii. Absolute lymphocyte count ≥ 150/uL iv. Hemoglobin ≥ 8 g/dL v. Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine within institutional norms for age (i.e.
- ≤ 2 mg/dL in adults or according to table below in children <18 years) OR creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
- Serum ALT/AST ≤ 3.0 ULN (grade 1)
- Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
- Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
- Baseline oxygen saturation > 92% on room air
- Pregnancy Test Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential) or NA
- 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 GD2CART cells are detectable in peripheral blood or CSF.
- Ability to give informed consent. All subjects ≥ 18 years of age must be able to give informed consent. For subjects <18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and written 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
- For Dose Escalation: Bulky tumor involvement of cerebellar vermis or hemispheres (pontocerebellar peduncles involvement is acceptable), or thalamic lesions that in the investigator's assessment place the subject at unacceptable risk for herniation.
- For Dose Expansion: Bulky disease that in the investigator's assessment place the subject at unacceptable risk for herniation. Thalamic DMG is permitted.
- Clinically significant swallowing dysfunction/dysphagia or prominent medullary dysfunction, as determined by the clinical investigator; or primary cervical cord tumors above C6/7 that represent a high risk of respiratory compromise, as determined by the clinical investigator.
- Current systemic corticosteroid therapy above physiologic replacement levels.
- Ongoing use of dietary supplements, alternative therapies or extreme diet modifications or any medication not approved by the investigators
- Prior CAR therapy.
- Prior immunomodulatory therapy, except for checkpoint inhibitor therapy after at least 3 month wash-out.
- Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable.
- Diagnosed ongoing infection with:
- HIV,
- 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.
- Clinically significant systemic illness or medical condition (e.g. significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
- Women who are pregnant or breastfeeding.
- 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.
- Known sensitivity or allergy to any agents/reagents used in this study.
- Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
- All subject files must include supporting documentation to confirm subject eligibility.
- The method of confirmation can include, but is not limited to, laboratory test results, radiology test results, subject self-report, and medical record review.
- *Anyone under 26, please contact Ashley Jacobs and anyone 26 and older, please contact Monica Reddy
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
Primary Objectives:
- Determine the feasibility of manufacturing autologous T cells transduced with 14g2a-CD8-BBz-iCasp9 retroviral vector expressing GD2 Chimeric Antigen Receptor (GD2CART) for administration in subjects with H3K27M-mutant diffuse midline glioma (DMG) using a retroviral vector and dasatinib in the Miltenyi CliniMACS Prodigy® system.
- Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), route and schedule of GD2CART and lymphodepleting chemotherapy in subjects with H3K27M-mutant DMG.
- Assess the safety of the MTD/RP2D, route and schedule of GD2CART in expansion cohorts of subjects with H3K27M-mutant DMG.
Secondary Objectives:
- In a preliminary manner, assess clinical benefit and Patient Reported Outcomes (PROs) of GD2CART at the RP2D in children and adults with H3K27M-mutant DMG.
- Evaluate the safety and impact on clinical benefit of repeat intracerebroventricular (ICV) administrations of GD2CART according to Arms A, B, C or D.
- If unacceptable toxicity occurs that is possibly, probably or likely related to GD2CART, assess the capacity for AP1903, a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants will undergo apheresis (collection of blood cells) so their T cells can be manufactured into GD2 CAR T cells. Depending on the assigned arm, you may receive a short course of chemotherapy (fludarabine and cyclophosphamide, and in some arms rituximab) before a hospitalized infusion of the CAR T cells either into a vein (intravenous) or directly into the brain ventricles (intracerebroventricular, ICV); some arms allow repeat ICV doses. You will have follow-up visits with brain/spine imaging at set time points, monitoring for side effects (with the option to give AP1903 to try to clear the engineered cells if treatment-related toxicity occurs), and complete questionnaires about symptoms and quality of life. Women of childbearing potential will have pregnancy testing and must agree to use contraception for a period after treatment while cells are detectable.
How the study is structured. Phase 1, non-randomized, open (not masked) interventional trial with multiple experimental arms. Participants receive their own (autologous) GD2 CAR T cells; arms differ by route (intravenous vs intracerebroventricular), by whether preparative lymphodepleting chemotherapy is given, and by dose levels. The study proceeds with dose-escalation cohorts and expansion cohorts to evaluate manufacturing success, immediate safety (dose‑limiting toxicities within 28 days), and selected clinical outcomes over follow-up.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Glioma of Spinal Cord; Glioma of Brainstem. Does it apply to my diagnosis?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Gaucher disease
Important dates
- Study start
- Jun 4, 2020
- Primary completion
- Jul 31, 2028 (estimated)
- Study completion
- Jul 31, 2043 (estimated)
- Target enrollment
- 97 participants (estimated)
- Last updated on registry
- Jan 26, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Stanford University
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- CureSearch
- National Cancer Institute (NCI)
- Alex's Lemonade Stand Foundation
- Parker Institute for Cancer Immunotherapy
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Ashley Jacobs, RN, BSN 📞 650-497-7533 ✉ gd2cart@stanfordchildrens.org
- Monica Reddy 📞 (650) 736-2690 ✉ secure-sci-cto-neuro-crcs-nio@lists.stanford.edu
Participating sites (1)
- Lucile Packard Children's Hospital (LPCH)Recruiting
Stanford, California, 94304 · United States
- Ashley Jacobs · 650-497-7533 · GD2CART@stanfordchildrens.org
- Monica Reddy · (650) 736-2690 · secure-sci-cto-neuro-crcs-nio@lists.stanford.edu
- Michelle Monje, MD, PHD
- Liora Schultz, MD
- Kara Davis, D.O.
- Crystal Mackall, MD
- Laura Prolo, M.D
- Sneha Ramakrishna, MD
- Cynthia Campen, MD
- Sonia Partap, MD
- Paul Fisher, MD
- Lindsey Rasmussen, MD
- Timothy Cornell, MD
- Susan Hiniker, MD
- Brian Scott, MD
- Katherine Ryan, MD
- Kun-Wei Song, MD
- Catherine Aftandilian, MD
- Chelsey Burke, MD
- Jay Balagtas, MD
- Saurabh Dahiya, MD
- Tanja Gruber, MD, Phd
- Mark Halverson, MD
- Claire Johns, MD
- Yong Kim, MD
- Norman Lacayo, MD
- Gordon Li, MD
- Michael Lim, MD
- Julie Ma, MD
- Lianna Marks, MD
- Raya Saab, MD
- Richard Sleightholm, MD
- Zachary Threlkeld, MD
- Wen-Kai Weng, MD, Phd
Terms used on this page · explanations by MedicalUpdates.ai
- primary purpose
- The main reason an interventional study is being done, for example treatment, prevention, diagnosis, supportive care or basic science.
- CAR T cells
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- Prior Therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Performance Status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- ANC
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- ECHO
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- ECG
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- Baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- LAR
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- assent
- A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
- Dose Escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- corticosteroid
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- wash-out
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- INCLUSION CRITERIA
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- EXCLUSION CRITERIA
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- maximum tolerated dose
- The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
- recommended phase 2 dose
- The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
- intracerebroventricular
- Given directly into the fluid-filled spaces (ventricles) inside the brain, usually through an implanted catheter or reservoir.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials