Anti-GD2 CAR T Cells in Pediatric Patients Affected by High Risk and/or Relapsed/Refractory Neuroblastoma or Other GD2-positive Solid Tumors

NCT03373097 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: GD2CAR01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and efficacy of GD2-CART01, a CAR T cell treatment targeting GD2 in paediatric or young adult patients with High Risk and/or relapsed/refractory Neuroblastoma. A small exploratory cohort of patients with GD2-positive tumors other than Neuroblastoma has also been included.

Conditions

Neuroblastoma; Neuroblastoma Recurrent; GD2-positive Solid Tumors; Osteosarcoma; Ewing Sarcoma; Sarcoma

Keywords

Neuroblastoma; GD2 CAR T cell; CAR T; GD2-positive solid tumors; Osteosarcoma; Ewing Sarcoma; GD2-positive sarcoma

Outcome Measures

Primary Outcomes (2)

• Phase I - Identification of the dose limiting toxicity (DLT)

  Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 4 and the number of patients experiencing DLT will be evaluated

  4 weeks after T cell infusion

• Phase II - Antitumor effect

  Assessment of Best Overall Response (BOR)

  Up to 6 months after T cell infusion

Secondary Outcomes (7)

• In vivo persistence/expansion of infused CAR T cell

  UP to 5 years

• Serum cytokine profiling

  First 2 weeks after T cell infusion

• Time To Progression (TTP)

  Up 5 years after T cell infusion

• Event-Free Survival (EFS)

  Up 5 years after T cell infusion

• Overall Survival (OS)

  Up 5 years after T cell infusion

Study Arms (1)

GD2-CART01

EXPERIMENTAL

After a lymphodepleting regimen the patients will receive 1.0 to 10.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells.

Biological: GD2-CART01

Interventions

GD2-CART01 BIOLOGICAL

Following a lymphodepleting treatment with conventional chemotherapy, patients will be treated with 1.0 to 10.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.

GD2-CART01

Eligibility Criteria

• Age: 12 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of NBL that have been treated with frontline therapy and is judged to be incurable, based upon the following criteria:
• Relapse after first-line treatment, proved by a positive 123-I-mMIBG-scan
• Persistence/progression of disease after the initiation of the upfront treatment
• Patients must have measurable or evaluable disease at the time of treatment enrollment, as shown by bone marrow biopsy/aspirate, US or CT/MRI scan or by 123-I-mMIBG scan.
• Recover from the toxic effect of previous chemotherapies: grade 4 and or 3 non-hematologic toxicities must have resolved to grade ≤2; if some effects of the therapies have become chronic (i.e. treatment associated thrombocytopenia), the patient must be clinically stable, according to the opinion of the treating physicians, and meet all other eligibility criteria.
• Age: 12 months -18 years.
• Voluntary informed consent is given. For subjects \< 18 years old their legal guardian must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
• Clinical performance status: Patients \> 16 years of age: Karnofsky greater than or equal to 60%; Patients less than or equal to 16 years of age: Lansky scale greater than or equal to 60%.
• Patients 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 months after receiving the preparative regimen.
• Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
• Phase II
• Diagnosis of NBL that have been treated with frontline therapy and is judged to be incurable, based upon the following criteria:
• Relapse after first-line treatment, proved by a positive MIBG-scan
• Persistence/progression of disease after the initiation of the upfront treatment
• Diagnosis of extremely High Risk NBL at high risk of relapse, defined by stage III/IV and Myc-N amplification, at the end of the first-line treatment according to the Standard of Care, even if NED.

You may not qualify if:

• Pregnant or lactating women
• Severe, uncontrolled active intercurrent infections
• Active hepatitis B or hepatitis C infection
• HIV infection
• Rapidly progressive disease with life-expectancy \< 6 weeks
• History of grade 3 or 4 hypersensitivity to murine protein-containing products
• 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: 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 PI would pose an unacceptable risk to the subject.
• Untreated CNS metastasis; patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
• Concurrent or recent prior therapies, before infusion:
• Systemic chemotherapy in the 2 weeks preceding infusion.

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

Related Publications (4)

• Locatelli F, Pagliara D, De Ioris MA, Becilli M, Del Baldo G, Serra A, Mastronuzzi A, Cefalo MG, Li Pira G, Leone G, Bertaina V, Fabozzi F, Di Nardo M, Rosignoli C, D'Andrea ML, Crocoli A, Vennarini S, Sinibaldi M, Di Cecca S, Guercio M, Iaffaldano L, Lucarelli B, Algeri M, Merli P, Colafati GS, De Angelis B, Quintarelli C, Del Bufalo F. GD2-targeting CAR T cells in high-risk neuroblastoma: a phase 1/2 trial. Nat Med. 2025 Nov;31(11):3689-3699. doi: 10.1038/s41591-025-03874-6. Epub 2025 Aug 21.

  PMID: 40841488 DERIVED

• Yeku OO, Longo DL. CAR T Cells for Neuroblastoma. N Engl J Med. 2023 Apr 6;388(14):1328-1331. doi: 10.1056/NEJMe2300317. No abstract available.

  PMID: 37018497 DERIVED

• Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, Mastronuzzi A, Cefalo MG, Pagliara D, Amicucci M, Li Pira G, Leone G, Bertaina V, Sinibaldi M, Di Cecca S, Guercio M, Abbaszadeh Z, Iaffaldano L, Gunetti M, Iacovelli S, Bugianesi R, Macchia S, Algeri M, Merli P, Galaverna F, Abbas R, Garganese MC, Villani MF, Colafati GS, Bonetti F, Rabusin M, Perruccio K, Folsi V, Quintarelli C, Locatelli F; Precision Medicine Team-IRCCS Ospedale Pediatrico Bambino Gesu. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. N Engl J Med. 2023 Apr 6;388(14):1284-1295. doi: 10.1056/NEJMoa2210859.

  PMID: 37018492 DERIVED

• Tumino N, Weber G, Besi F, Del Bufalo F, Bertaina V, Paci P, Quatrini L, Antonucci L, Sinibaldi M, Quintarelli C, Maggi E, De Angelis B, Locatelli F, Moretta L, Vacca P, Caruana I. Polymorphonuclear myeloid-derived suppressor cells impair the anti-tumor efficacy of GD2.CAR T-cells in patients with neuroblastoma. J Hematol Oncol. 2021 Nov 12;14(1):191. doi: 10.1186/s13045-021-01193-0.

  PMID: 34772439 DERIVED

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma; Sarcoma, Ewing; Sarcoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Haematology-Oncology Department Chief

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: December 14, 2017
• Study Start: January 5, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 5, 2025

Record last verified: 2025-02

Locations

IT (1)