CAR T cell therapy targeting GD2 for neuroblastoma in children

Multi-modular Chimeric Antigen Receptor Targeting GD2 in Neuroblastoma

This study is testing a new treatment using modified immune cells to see if it can help children and teenagers with hard-to-treat neuroblastoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 1 Year to 16 Years
• Sex: All
• Sponsor: University College, London (Academic / other)
• Drugs / interventions: rituximab, CAR T, chemotherapy, Cyclophosphamide, Fludarabine
• Locations: 1 site (London)
• Trial ID: NCT05990751 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and feasibility of using GD2 CAR T cells in children and teenagers aged 1-16 years with relapsed or refractory neuroblastoma. Participants will undergo a procedure to collect their T cells, which will then be modified to target GD2 on neuroblastoma cells. Following this, patients will receive lymphodepleting chemotherapy before the modified T cells are infused. The study aims to monitor the engraftment, expansion, and persistence of these CAR T cells in the patients over a year.

Who should consider this trial

Good fit: Ideal candidates are children and teenagers aged 1-16 years with relapsed or refractory neuroblastoma.

Not a fit: Patients with only bone marrow detectable disease or those who have not had prior salvage chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for children with difficult-to-treat neuroblastoma.

How similar studies have performed: Previous studies using CAR T cell therapies for neuroblastoma have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 1 and ≤ 16 years.
2. 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.
3. Disease which has relapsed after or is refractory to at least one line of salvage combination chemotherapy.
4. 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.
5. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial.
6. 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.
7. Creatinine ≤1.5 ULN for age, if higher, an estimated (calculated) creatinine clearance must be ≥ 60 ml/min/1.73 m2.
8. Absolute lymphocyte count ≥ 0.25 x 10\^9/L.
9. For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable).
10. Written informed consent.

Exclusion Criteria:

1. 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.
2. Patients with active, inoperative CNS disease including leptomeningeal disease.
3. Active hepatitis B, C or HIV infection.
4. Inability to tolerate leukapheresis.
5. 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.
6. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC.
7. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.
8. Known allergy to albumin, EDTA or DMSO.
9. 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.
10. Prior treatment with investigational or approved gene therapy or cell therapy products.
11. Life expectancy \<3 months.
12. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to of GD2 CAR T cells infusion.
13. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of GD2 CAR T cells infusion.
14. Post-pubertal subjects who are pregnant or breastfeeding.

Exclusion criteria for the ATIMP infusion:

1. 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.
2. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of GD2 CAR T cells infusion.
3. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to GD2 CAR T cell infusion

Where this trial is running

London

• Great Ormond Street Hospital — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: MAGNETO Trial Coordinator

Conditions Neuroblastoma; neuroblastoma; CAR T cells