GD2-CAR T Cells for Pediatric Brain Tumours

NCT ID: NCT05298995

Last Updated: 2025-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-09

Study Completion Date

2038-11-30

Brief Summary

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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

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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

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Brain Tumor, Pediatric Medulloblastoma, Childhood Embryonal Tumor High Grade Glioma Diffuse Midline Glioma Diffuse Intrinsic Pontine Glioma Brain Tumor Adult

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARM A: MB/other embryonal tumor

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.

Group Type EXPERIMENTAL

GD2-CART01 (iC9-GD2-CAR T-cells)

Intervention Type 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

ARM B: Hemispheric HGG

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.

Group Type EXPERIMENTAL

GD2-CART01 (iC9-GD2-CAR T-cells)

Intervention Type 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

ARM C: Thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B

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.

Group Type EXPERIMENTAL

GD2-CART01 (iC9-GD2-CAR T-cells)

Intervention Type 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

Interventions

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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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Imaging assessments performed within 14 days of start of treatment
2. Age: 6months-30years
3. Measurable or evaluable disease on at least 2 dimensions on MRI at the time of treatment enrollment
4. Karnofsky/Lansky≥60
5. 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
6. 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)
7. 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
8. 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
9. Females of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus

Exclusion Criteria

1. Pregnant or lactating women
2. Severe,uncontrolledactiveinfections
3. HIV or active HCV and/or HBV infection
4. Rapidly progressive disease with life expectancy \< 6 weeks
5. Historyofgrade3or4hypersensitivitytomurineprotein-containingproducts
6. 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
7. Renal function: serum creatinine \> 3x ULN for age
8. Blood oxygen saturation \< 90%
9. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO
10. Marrow function: absolute neutrophils count (ANC) lower than 500/mm3 and/or platelets lower than 20.000 (not reached by transfusion)
11. 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:

1. 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
2. Systemic chemotherapy in the 3 weeks preceding infusion
3. Immunosuppressive agents less than or equal to 30 days
4. Radiation therapy must have been completed at least 6 weeks prior to enrollment
5. 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)
Minimum Eligible Age

6 Months

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Franco Locatelli

Head of the Department of Pediatric Hematology/Oncology and Cell and Gene Therapy

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ospedale Pediatrico Bambino Gesù

Roma, Italy, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Francesca Del Bufalo, MD

Role: CONTACT

00396859 ext. 2739

Angela Mastronuzzi, MD, PhD

Role: CONTACT

00396859 ext. 4647

Facility Contacts

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Francesca del Bufalo, MD PhD

Role: primary

0039-066859 ext. 2739

Angela Mastronuzzi, MD PhD

Role: backup

0039-066859 ext. 4647

Other Identifiers

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GD2CAR02

Identifier Type: -

Identifier Source: org_study_id

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