GD2-CAR T Cells for Pediatric Brain Tumours

NCT05298995 | Recruiting Phase 1

• 1 other identifier: GD2CAR02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• 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

  4 weeks after CAR T cell infusion

Secondary Outcomes (8)

• In vivo expansion and persistence

  Up to 5 years

• Tumor infiltration

  Up to 5 years

• iC9-GD2-CAR-T cells clearance after AP1903 infusion

  Up to 5 years

• Serum cytokine profiling

  Up to 3 months

• Time to progression (TTP)

  Up to 5 years

Study Arms (3)

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.

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.

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.

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

Interventions

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

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

Eligibility Criteria

• Age: 6 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

Ospedale Pediatrico Bambino Gesù

Roma, Italy, 00165, Italy

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Glioma; Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms

Central Study Contacts

Francesca Del Bufalo, MD

CONTACT

00396859; francesca.delbufalo@opbg.net

Angela Mastronuzzi, MD, PhD

CONTACT

00396859; angela.mastronuzzi@opbg.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department of Pediatric Hematology/Oncology and Cell and Gene Therapy

Study Record Dates

• First Submitted: March 18, 2022
• First Posted: March 28, 2022
• Study Start: November 9, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2038
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)