Actively Recruiting

Phase 1
Age: 0 - 16Years
All Genders
ID05544526

Chimeric Antigen Receptor (CAR)-T Cells to Target GD2 for Diffuse Midline Glioma in Children and Young Adults

Led by University College, London · Updated on 2023-09-11

12

Participants Needed

1

Research Sites

730 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

The trial investigates GD2CAR T-cell therapy in children and young adults aged 2 to 16 years with Diffuse Midline Glioma (DMG), a type of brain tumor. It is a Phase I clinical trial focused on assessing the safety, tolerability, and feasibility of this advanced therapy. Researchers also aim to understand how well the GD2CAR T-cells engraft, expand, and persist in patients following treatment. Participants will undergo a process to collect their T-cells through leucapheresis, which are then modified to produce GD2CAR T-cells over about 15 days. Before treatment, patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The GD2CAR T-cells are given intravenously at one of three dose levels. Patients who show no or partial response may receive a second treatment with CD19CAR T-cells administered directly into the brain via an Ommaya catheter. During the study, patients are monitored as inpatients for 2 to 4 weeks after infusion. Follow-up visits continue for one year with assessments every 6 weeks then every 3 months. If the disease returns within the first year, patients enter annual follow-up until the trial ends. All participants will be followed long term until the study concludes. The trial measures safety through toxicity rates and evaluates the success of producing the therapy, as well as patient survival and disease progression over one year.

CONDITIONS

Brief Title

CAR T Cells to Target GD2 for DMG

Who Can Participate

Age: 0 - 16Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 2 and 16 years
  • Diagnosis of H3K27M mutant Diffuse Midline Glioma confirmed by tissue
  • Tumor visible by imaging and restricted to brain stem or spinal cord
  • Completed radiation therapy at least 6 weeks prior
  • At least 3 weeks or 5 half-lives since treatment with other early phase trial agents
  • Karnofsky or Lansky performance score of 40% or higher
  • Absolute neutrophil count of 1.5 x 10^9/L or higher and platelet count of 100 x 10^9/L or higher
  • Total bilirubin less than 1.5 times the upper limit of normal
  • ALT less than 2.5 times the upper limit of normal
  • Serum creatinine less than 1.5 times the upper limit of normal for age
  • Agreement to pregnancy testing and contraception if post-pubertal
  • Written informed consent provided
Not Eligible

You will not qualify if you...

  • Taking systemic corticosteroids at 0.05 mg/kg dexamethasone daily or higher at time of CAR T cell infusion
  • Tumor involving thalamus, supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement allowed)
  • Signs of true tumor progression clinically or radiologically
  • Active hepatitis B, C, or HIV infection
  • Unable to tolerate leukapheresis
  • Significant neurological disorders unrelated to DMG
  • Serious systemic illness or organ dysfunction affecting safety or assessment
  • Contraindications to lymphodepletion, cyclophosphamide, fludarabine, anticoagulant citrate dextrose solution, or catheter insertion
  • Known allergies to albumin, DMSO, or EDTA
  • Primary immunodeficiency or autoimmune disease requiring recent systemic immunosuppression
  • Prior gene or cell therapy treatments
  • Life expectancy less than 3 months
  • Rituximab use within last 3 months
  • Pregnant or breastfeeding if post-pubertal

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - Approximately 15 days

Participants undergo unstimulated leukapheresis to collect T-cells for manufacturing the investigational therapy, which takes approximately 15 days.

1 to 2 visits depending on leukapheresis scheduling

Treatment

Duration - Lymphodepleting chemotherapy over 6 days; infusion followed by 2-4 weeks inpatient monitoring

Participants receive lymphodepleting chemotherapy followed by infusion of GD2 CAR T-cells. Placement of an intraventricular catheter (Ommaya catheter) occurs prior to infusion to allow monitoring and treatment if necessary.

Multiple visits over chemotherapy and infusion period plus inpatient monitoring for 2 to 4 weeks

Interventional Follow-up

Duration - 1 year

After discharge, participants are followed up for 1 year with visits to monitor response and safety, including a visit at 6 weeks post-infusion and then every 3 months.

Visits at 6 weeks post infusion then every 3 months until 1 year

Long-term Follow-up

Duration - Until end of trial

Participants enter long-term follow-up after the 1-year interventional phase to monitor health until the end of the trial.

Annual visits if relapse occurs within first year; otherwise timing may vary

Trial Site Locations

Total: 1 location

1

Great Ormond Street Hospital

London, United Kingdom

Actively Recruiting

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Research Team

C

CARMIGO Trial Coordinator

K

Karin Straathof

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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