Multi-modular Chimeric Antigen Receptor Targeting GD2 in Neuroblastoma

NCT05990751 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: UCL\142424
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

MAGNETO is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and teenagers aged 1-16 years with relapsed or refractory neuroblastoma. The study will assess the feasibility of generating the ATIMP (GD2 CAR T cells) and the safety of administering the ATIMP in patients with relapsed or refractory neuroblastoma.

Conditions

Neuroblastoma

Keywords

neuroblastoma; CAR T cells

Outcome Measures

Primary Outcomes (2)

• Safety of administering the ATIMP

  Incidence of grade 3-5 toxicity causally related to the ATIMP, particularly severe cytokine release syndrome and severe neurotoxicity.

  28 days

• Number of therapeutic products generated and the number of ATIMPs infused after successful manufacture

  Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture.

  28 days

Secondary Outcomes (4)

• Objective response rate

  1 year

• Progression Free Survival (PFS)

  1 year

• Time to Progression (TTP)

  1 year

• Overall survival

  1 year

Study Arms (1)

GD2 CAR T cells

EXPERIMENTAL

Treatment with GD2 CAR T cells

Biological: GD2 CAR T cells

Interventions

GD2 CAR T cells BIOLOGICAL

The GD2 CAR T cells target GD2 positive cells. The cells also express transgenes that aim to increase their resistance within the tumour microenvironment.

GD2 CAR T cells

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 1 and ≤ 16 years.
• Tissue diagnosis of neuroblastoma. If sufficient biopsy material is available, GD2 expression on the tumour will be confirmed. As GD2 is consistently expressed in neuroblastoma demonstration of GD2 is not mandated.
• Disease which has relapsed after or is refractory to at least one line of salvage combination chemotherapy.
• Measurable disease by cross sectional imaging or evaluable disease by uptake on 123I-MIBG scan. Patients with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study.
• At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial.
• Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≥ 50%. Patients who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
• Creatinine ≤1.5 ULN for age, if higher, an estimated (calculated) creatinine clearance must be ≥ 60 ml/min/1.73 m2.
• Absolute lymphocyte count ≥ 0.25 x 10\^9/L.
• For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable).
• Written informed consent.

You may not qualify if:

• Patients with only bone marrow detectable disease in the absence of measurable disease by cross sectional imaging or evaluable disease by uptake on 123I-MIBG scan.
• Patients with active, inoperative CNS disease including leptomeningeal disease.
• Active hepatitis B, C or HIV infection.
• Inability to tolerate leukapheresis.
• Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
• Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC.
• Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.
• Known allergy to albumin, EDTA or DMSO.
• Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease modifying agents within the last 2 years.
• Prior treatment with investigational or approved gene therapy or cell therapy products.
• Life expectancy \<3 months.
• Use of rituximab (or rituximab biosimilar) within the last 3 months prior to of GD2 CAR T cells infusion.
• Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of GD2 CAR T cells infusion.
• Post-pubertal subjects who are pregnant or breastfeeding.
• Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable at the time of scheduled GD2 CAR T cells infusion.

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Great Ormond Street Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Neuroblastoma

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2023
• First Posted: August 14, 2023
• Study Start: April 19, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2041
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

GB (1)