Brief Summary
The aim of this study is to assess the toxicity, efficacy, and optimum dosing of autologous GD2-specific chimeric antigen receptor-expressing T cells (GD2-iCAR-PBT, a cell product infusion derived from the patient’s own T cells) in paediatric patients with Diffuse Midline Glioma.
Intervention/Treatment
- Drug: GD2-iCAR-PBT
Inclusion Criteria
PART I Inclusion Criteria
- Age less than or equal to 21 years old at the time of study enrolment;
- Diffuse Intrinsic Pontine Glioma (DIPG) diagnosed by MRI and/or histological diagnosis of Diffuse Midline Glioma (DMG) with an H3K27M mutation or loss of H3K27 trimethylation;
- Lansky / Karnofsky score greater than or equal to 50%;
- Absolute lymphocyte count greater than or equal to 0.1×10^9/L;
- No evidence of tumour progression following any form of anti-tumour treatment;
- Life expectancy of greater than or equal to 12 weeks.
PART II Inclusion Criteria
- At least 4 weeks since completion of treatment with radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells of at least 50Gy to the primary tumour;
- Previously enrolled on Part I with availability of T cell product that has met batch release criteria including greater than or equal to 20% expression of GD2-iCAR (by flow cytometry) on the autologous peripheral blood T cells (PBT);
- Karnofsky greater than or equal to 50% for patients greater than 16 years of age and Lansky greater than or equal to 50% for patients less than or equal to 16 years of age;
- Recovered to less than or equal to Grade 1 from the acute toxic effects of all prior anti-cancer treatment at least a week before entering this study;
- Life expectancy of greater than or equal to 6 weeks;
- At least 4 weeks since major surgery, and recovered adequately from the toxicity and/or complications from surgery;
- Adequate cardiac function, defined as fractional shortening greater than or equal to 27% or ejection fraction of greater than or equal to 50%, measured by echocardiography;
- Females of childbearing potential and fertile male patients must use an effective method of contraception starting with the first dose of study therapy through 4 months after the last dose of study therapy;
- For females of childbearing potential, the patient must have a negative serum pregnancy test at screening, and a negative urine pregnancy test, prior to dosing at each treatment course.