ClinicalTrials.gov record NCT05298995
GD2-CAR T Cells for Pediatric Brain Tumours
Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T Cells in Pediatric and Young Adult Patients Affected by Relapsed/Refractory Central Nervous System Tumors
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 I, non-randomized study testing autologous iC9-GD2 CAR T cells in pediatric and young adult patients with relapsed or refractory malignant central nervous system tumors. Patients undergo leukapheresis to make the CAR T product, receive a lymphodepleting chemotherapy regimen, then a single IV infusion of GD2-CART01; the product includes an inducible suicide gene (iC9). The study enrolls three arms based on tumor histology/location and includes active follow-up for 5 years plus a 15-year regulatory follow-up for gene therapy recipients.
What it is studying. The study is testing the safety and feasibility of giving a single infusion of autologous iC9-GD2 CAR T cells after lymphodepleting chemotherapy. It aims to define dose-limiting toxicities and a recommended dose, and to measure how the infused cells expand, persist, infiltrate tumor tissue, and are cleared after giving the activating agent (AP1903) for the suicide switch. The study will also collect clinical outcome measures such as time to progression, event-free survival, overall survival, and tumor response by RAPNO criteria, and will evaluate serum and CSF cytokine profiles.
What the researchers hope to learn. 1. Determine the safety profile and the maximum tolerated dose or recommended dose of iC9-GD2 CAR T cells. 2. Measure in vivo expansion and long-term persistence of the infused CAR T cells in blood and cerebrospinal fluid. 3. Assess tumor infiltration by the infused T cells and kinetics of cell clearance after activating the iC9 suicide switch. 4. Characterize serum and CSF cytokine patterns and record clinical outcomes (time to progression, event-free survival, overall survival) and tumor responses by RAPNO criteria.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The purpose of this study is to test the safety and efficacy of iC9-GD2-CAR T-cells, a third generation (4.1BB-CD28) CAR T cell treatment targeting GD2 in paediatric or young adult patients affected by relapsed/refractory malignant central nervous system (CNS) tumors. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Biological
- GD2-CART01 (iC9-GD2-CAR T-cells)
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Imaging assessments performed within 14 days of start of treatment
- Age: 6months-30years
- Measurable or evaluable disease on at least 2 dimensions on MRI at the time of treatment enrollment
- Karnofsky/Lansky≥60
- Recoverfromthetoxiceffectsofpreviousradiationandchemotherapies:grade4and or 3 non-hematologic toxicities must have resolved to grade ≤ 2; in presence of chronic complications (i.e. treatment-associated thrombocytopenia), patient must be clinically stable, according to the opinion of the treating physicians, and meet all other eligibility criteria
- Positioning of an implantable intraventricular access device (CodmanHolterRickham reservoir, Integra LifeSciences, NJ, U.S.A) and a microdialysis probe (71 high cutoff microdialysis bolt catheter, M Dialysis AB, Stockholm Sweden)
- Written and signed informed consent from patients, parents or legal guardians. For subjects < 18 year-old their legal guardian must give informed consent. In addition, pediatric subjects will be included in age-appropriate discussion and written informed assent will be obtained for those greater than or equal to 7 years of age, when appropriate
- Patients of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
- Females of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus
Exclusion criteria
- Pregnant or lactating women
- Severe,uncontrolledactiveinfections
- HIV or active HCV and/or HBV infection
- Rapidly progressive disease with life expectancy < 6 weeks
- Historyofgrade3or4hypersensitivitytomurineprotein-containingproducts
- Hepatic function: inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN based on age and laboratory specific normal ranges
- Renal function: serum creatinine > 3x ULN for age
- Blood oxygen saturation < 90%
- Cardiac function: left ventricular ejection fraction lower than 45% by ECHO
- Marrow function: absolute neutrophils count (ANC) lower than 500/mm3 and/or platelets lower than 20.000 (not reached by transfusion)
- Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the principal investigator (PI) would pose an unacceptable risk to the subject. 12.Concurrent or recent prior therapies, before infusion:
- If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to infusion. Recent or current use of inhaled/topical/non- absorbable steroids is not exclusionary. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis
- Systemic chemotherapy in the 3 weeks preceding infusion
- Immunosuppressive agents less than or equal to 30 days
- Radiation therapy must have been completed at least 6 weeks prior to enrollment
- Otheranti-neoplasticinvestigationalagentscurrentlyorwithin30dayspriorto start of protocol therapy
- Patient-derived GD2-CART01 production failure: vitality <80%, CD3+ cells <80%, CD3+ CAR+ cells <20%, CD3+ CAR+ antitumor activity <60% in functional co-culture assay at an Effector: Target ratio 1:1, viable CAR+ cells upon AP1903 exposition >20%, RCR positivity, Vector Copy Number >10, non-sterility, endotoxin contamination (> 1 EU/ml)
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
The study will consist of a Phase I, dose escalation phase aimed at evaluating the safety and feasibility of intravenous injections of autologous iC9-GD2-CAR T-cells in patients with refractory/relapsed malignant CNS tumors. Considering the peculiar potential risks associated with the treatment of CNS tumors, the study has been designed to enrol patients in 3 different arms depending on the histology and location of the disease. This model of enrollment is aimed at testing the safety sequentially, starting from categories of patients at lower risk of severe intracranial hypertension first, and subsequently proceeding with patients at proportionally increased risk. In particular, the three arms explored will be relapsed or refractory:
- ARM A: MB/other embryonal tumor
- ARM B: Hemispheric HGG
- ARM C: Thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B
Eligible patients will undergo leukapheresis in order to harvest T cells, which will be manufactured to obtain the autologous CAR T product iC9-GD2-CAR T-cells, a GD2-targeting CAR T product. Briefly, the patients will be treated with a lymphodepleting regimen containing conventional chemotherapic agents and subsequently will receive a single infusion of GD2-CART01. Moreover, the product contains a suicide gene safety switch (namely inducible Caspase 9): in case of relevant toxicities, the patient will receive the dimerizing agent in order to activate the apoptotic pathway in the infused T cells. After infusion of CAR T cells, the patients will enter a 5-year active follow-up period (for disease follow-up). A conventional 15-year follow-up will be performed as per regulatory requirements in patients receiving gene therapy.
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 have T cells collected by leukapheresis and must have an intraventricular reservoir and a microdialysis probe placed. They will receive a lymphodepleting chemotherapy regimen, then a single intravenous infusion of the autologous iC9‑GD2‑CAR T‑cell product. After infusion there will be close monitoring with blood and cerebrospinal fluid (CSF) tests and repeated MRI scans; the protocol allows giving AP1903 to activate the suicide switch in the CAR T cells if severe toxicity occurs. Participants enter active disease follow‑up for 5 years and a longer 15‑year regulatory follow‑up for gene‑therapy recipients.
How the study is structured. Phase I interventional treatment trial with a non-randomized, single-group dose-escalation design. Patients are enrolled into one of three arms based on tumor type and location. Participants give blood by leukapheresis for manufacturing of autologous CAR T cells, receive a preparative (lymphodepleting) chemotherapy regimen, then one intravenous infusion of GD2-CART01. Safety and biological measures are followed closely, with active disease follow-up for up to 5 years and a 15-year regulatory follow-up after gene therapy.
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 Brain Tumor, Pediatric; Medulloblastoma, Childhood; Embryonal Tumor; High Grade Glioma; Diffuse Midline Glioma; Diffuse Intrinsic Pontine Glioma; Brain Tumor Adult. 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 Italy. 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
- Nov 9, 2023
- Primary completion
- November 2027 (estimated)
- Study completion
- November 2038 (estimated)
- Target enrollment
- 54 participants (estimated)
- Last updated on registry
- Sep 30, 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
- Bambino Gesù Hospital and Research Institute
- Principal investigator
- Franco Locatelli, Head of the Department of Pediatric Hematology/Oncology and Cell and Gene Therapy
Bambino Gesù Hospital and Research Institute
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.
- Francesca Del Bufalo, MD 📞 00396859 ext. 2739 ✉ francesca.delbufalo@opbg.net
- Angela Mastronuzzi, MD, PhD 📞 00396859 ext. 4647 ✉ angela.mastronuzzi@opbg.net
Participating sites (1)
- Ospedale Pediatrico Bambino GesùRecruiting
Roma, Italy, 00165 · Italy
- Francesca del Bufalo, MD PhD · 0039-066859 ext. 2739 · francesca.delbufalo@opbg.net
- Angela Mastronuzzi, MD PhD · 0039-066859 ext. 4647 · angela.mastronuzzi@opbg.net
- Franco Locatelli, MD PhD
Terms used on this page · explanations by MedicalUpdates.ai
- CAR T
- 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.
- relapsed/refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- 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.
- eligibility criteria
- The rules the study team uses to decide who may take part. They are usually split into inclusion criteria and exclusion criteria.
- intraventricular
- Given directly into the fluid-filled spaces (ventricles) inside the brain, usually through an implanted catheter or reservoir.
- 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.
- legal guardian
- 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.
- 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.
- life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- upper limit of normal
- 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.
- 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.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- glucocorticoids
- 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.
- Immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- 1:1
- How many participants go to each group. In a 2:1 ratio, two are assigned to the first group for every one assigned to the second.
- 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.
- dose escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- relapsed
- A condition that improved with treatment and has since returned or worsened.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
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.
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