Brain Tumor, PediatricPhase 1NCT05298995
GD2-CAR T Cells for Pediatric Brain Tumours
A Phase 1 study testing GD2-CART01 (iC9-GD2-CAR T-cells) in people with Brain Tumor, Pediatric and Medulloblastoma, Childhood, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 months to 30 years
- Conditions the study is for
- Brain Tumor, Pediatric, Medulloblastoma, Childhood, Embryonal Tumor
- What is being tested?
- GD2-CART01 (iC9-GD2-CAR T-cells)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteItaly
- Study dates
- 9 Nov 2023to Nov 2038
- 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 6 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
- 13.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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Ospedale Pediatrico Bambino Gesù
Roma, Italy, 00165
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
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Brain Tumor, Pediatric, Medulloblastoma, Childhood, Embryonal Tumor, High Grade Glioma, Diffuse Midline Glioma, Diffuse Intrinsic Pontine Glioma
- Being tested
- GD2-CART01 (iC9-GD2-CAR T-cells)
- Keywords
- Brain tumors, high grade glioma, medulloblastoma, Diffuse Midline Glioma, Diffuse Intrinsic Pontine Glioma, CAR T cell, GD2-antigen, Immunotherapy, Pediatric Central Nervous System tumours, Central nervous system tumour young adults
- Medical subject headings
- Brain Neoplasms, Medulloblastoma, Neoplasms, Germ Cell and Embryonal, Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GD2-CART01 (iC9-GD2-CAR T-cells)Biological
Following a lymphodepleting treatment with conventional chemotherapy, patients will be treated with 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells, infused i.v. as a single dose
| Study group | Role | What they receive |
|---|---|---|
| ARM A: MB/other embryonal tumor | Experimental | After a lymphodepleting regimen, patients affected by relapsed/refractory MB/other embryonal tumor will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. Receives: Biological: GD2-CART01 (iC9-GD2-CAR T-cells) |
| ARM B: Hemispheric HGG | Experimental | After a lymphodepleting regimen, patients affected by relapsed/refractory hemispheric high grade glioma will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. Receives: Biological: GD2-CART01 (iC9-GD2-CAR T-cells) |
| ARM C: Thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B | Experimental | After a lymphodepleting regimen, patients affected by relapsed/refractory thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. Receives: Biological: GD2-CART01 (iC9-GD2-CAR T-cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and definition of the MTD/RD
To evaluate the safety of the infusion of iC9-GD2-CAR-T cells at different escalating/de-escalating doses and establish the dose limiting toxicity (DLT) and the maximum tolerated dose/recommended dose (MTD/RD) of the cellular product
Measured: 4 weeks after CAR T cell infusion
Secondary outcomes (8)
In vivo expansion and persistence
To assess the in vivo persistence and expansion of the infused CAR T-cells in the peripheral blood (PB) and CSF using immunoassays and transgene detection (Droplet PCR), both for the whole population and the specific T cells subsets
Measured: Up to 5 years
Tumor infiltration
To evaluate the tumor infiltration of the infused T cells by immunohistochemistry (IHC), flow cytometry and/or transgene detection (Droplet PCR), whenever the tumor sample is available after the treatment
Measured: Up to 5 years
iC9-GD2-CAR-T cells clearance after AP1903 infusion
To assess the kinetic of iC9-GD2-CAR-T cells clearance after AP1903 infusion
Measured: Up to 5 years
Serum cytokine profiling
To define the serum and CSF cytokine profile and its correlation with CRS in order to identify a possible predictive profile
Measured: Up to 3 months
Time to progression (TTP)
To evaluate the TTP after infusion
Measured: Up to 5 years
Event-free survival (EFS)
To evaluate the EFS after infusion
Measured: Up to 5 years
Overall survival (OS)
To evaluate the OS after infusion
Measured: Up to 5 years
Disease outcome according to the Response assessment in pediatric neuro-oncology (RAPNO) criteria
umor response assessment through the RAPNO criteria
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2022
- Study start9 Nov 2023
- Primary completionNov 2027 (estimated)
- Study completionNov 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Tumor, PediatricStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bambino Gesù Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Franco Locatelli, Bambino Gesù Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05298995
- Sponsor's protocol ID
- GD2CAR02
- Status last verified
- Sep 2026
- First submitted
- 18 Mar 2022
- Last updated
- 30 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05298995
- Acronym / sponsor ID
- GD2CAR02
- Conditions
- Brain Tumor, Pediatric, Medulloblastoma, Childhood, Embryonal Tumor, High Grade Glioma, Diffuse Midline Glioma, Diffuse Intrinsic Pontine Glioma
- Keywords
- Brain tumors, high grade glioma, medulloblastoma, Diffuse Midline Glioma, Diffuse Intrinsic Pontine Glioma, CAR T cell, GD2-antigen, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Bambino Gesù Hospital and Research InstituteUniversity, hospital or other
- Study start
- 9 Nov 2023 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2038 (estimated)
- First posted
- 28 Mar 2022 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ARM A: MB/other embryonal tumor | Experimental | Biological: GD2-CART01 (iC9-GD2-CAR T-cells)After a lymphodepleting regimen, patients affected by relapsed/refractory MB/other embryonal tumor will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. |
| ARM B: Hemispheric HGG | Experimental | Biological: GD2-CART01 (iC9-GD2-CAR T-cells)After a lymphodepleting regimen, patients affected by relapsed/refractory hemispheric high grade glioma will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. |
| ARM C: Thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B | Experimental | Biological: GD2-CART01 (iC9-GD2-CAR T-cells)After a lymphodepleting regimen, patients affected by relapsed/refractory thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B will receive 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells. |
Who may qualify
- Ages
- 6 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- Pregnant or lactating women
- Severe,uncontrolledactiveinfections
- HIV or active HCV and/or HBV infection
- Rapidly progressive disease with life expectancy < 6 weeks
- Historyofgrade3or4hypersensitivitytomurineprotein-containingproducts
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 |
|---|---|---|
| GD2-CART01 (iC9-GD2-CAR T-cells)Following a lymphodepleting treatment with conventional chemotherapy, patients will be treated with 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells, infused i.v. as a single dose | Biological | 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 |
Primary outcome
Safety and definition of the MTD/RD
Time frame: 4 weeks after CAR T cell infusion
To evaluate the safety of the infusion of iC9-GD2-CAR-T cells at different escalating/de-escalating doses and establish the dose limiting toxicity (DLT) and the maximum tolerated dose/recommended dose (MTD/RD) of the cellular product
8 secondary outcomes
In vivo expansion and persistence
Time frame: Up to 5 years
Tumor infiltration
Time frame: Up to 5 years
iC9-GD2-CAR-T cells clearance after AP1903 infusion
Time frame: Up to 5 years
Serum cytokine profiling
Time frame: Up to 3 months
Time to progression (TTP)
Time frame: Up to 5 years
Event-free survival (EFS)
Time frame: Up to 5 years
Overall survival (OS)
Time frame: Up to 5 years
Disease outcome according to the Response assessment in pediatric neuro-oncology (RAPNO) criteria
Time frame: Up to 5 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 30 Sep 2026.
- Individual participant dataSharing planned: No
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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.
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 GD2-CART01 (iC9-GD2-CAR T-cells) in people with Brain Tumor, Pediatric and Medulloblastoma, Childhood, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.
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 9 inclusion and 17 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 30 Sep 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 Italy. 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 Francesca Del Bufalo, MD (00396859 ext. 2739, francesca.delbufalo@opbg.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and definition of the MTD/RD (time frame: 4 weeks after CAR T cell infusion). 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 30 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.