CAR T Cells to Target GD2 for DMG

NCT05544526 | Recruiting Phase 1 DMC

• 1 other identifier: UCL/ 150853
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The CARMIGO Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults aged 2-16 years with Diffuse Midline Glioma (DMG). The study will evaluate the feasibility of generating the ATIMP, the safety and tolerability of the GD2CAR T-cell therapy and how effectively GD2CAR T-cells engraft, expand and persist following administration in patients with DMG.

Conditions

Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

CAR T cells; Diffuse Midline Glioma; DMG

Outcome Measures

Primary Outcomes (2)

• Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP

  Toxicity of GD2 CAR T cells as assessed by the incidence of grade 3-5 toxicity causally related to the ATIMP (particularly severe cytokine release syndrome and severe neurotoxicity).

  28 days

• Feasibility of manufacturing GD2 CAR T-cells evaluated by the number of therapeutic products generated

  Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused (as an intravenous agent (Theme 1) and as an intraventricular agent (Theme 2) after successful manufacture.

  28 days

Secondary Outcomes (4)

• Overall survival (OS)

  1 year

• Progression Free Survival (PFS)

  1 year

• Time to Progression (TTP)

  1 year

• Best objective response rate (ORR)

  1 year

Study Arms (1)

GD2 CAR T Cells

EXPERIMENTAL

Treatment with the ATIMP: GD2 CAR T-cells

Biological: GD2 CAR T cells

Interventions

GD2 CAR T cells BIOLOGICAL

Infusion with: GD2 CAR T-cells

GD2 CAR T Cells

Eligibility Criteria

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

You may qualify if:

• Age ≥ 2 and ≤ 16 years
• Tissue diagnosis of H3K27M mutant Diffuse Midline Glioma.
• Radiographically evident tumour restricted to the brain stem or spinal cord.
• At least 6 weeks following completion of radiation therapy.
• 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 ≥ 40% allowing for stable neurological deficit due to DMG
• Absolute neutrophil count ≥1.5 x109/L and platelet count ≥ 100 x109/L
• Total bilirubin \< 1.5 ULN and ALT \< 2.5 ULN
• Serum creatine \< 1.5 ULN for age.
• For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable)
• Written informed consent

You may not qualify if:

• Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of RQR8/huK28Z CAR T cell infusion
• Tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed)
• Clinical or radiological evidence of true tumour progression
• Active hepatitis B, C or HIV infection
• Inability to tolerate leukapheresis
• Pre-existing significant neurological disorder not related to DMG
• 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
• Any contraindication to Ommaya reservoir insertion (or similar catheter)
• Known allergy to albumin, DMSO or EDTA
• 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 RQR8/huK28Z CAR T cell infusion

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

Central Study Contacts

CARMIGO Trial Coordinator

CONTACT

0207 679 9599; ctc.CARMIGO@ucl.ac.uk

Karin Straathof

CONTACT

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: September 13, 2022
• First Posted: September 16, 2022
• Study Start: August 15, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2039
• Last Updated: September 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)