A Phase I Study of the Safety of Autologous GD2-Specific Chimeric Antigen Receptor-Expressing T Cells in Children with Diffuse Midline Glioma

Intervention/Treatment

• Drug: GD2-iCAR-PBT

Inclusion Criteria

PART I Inclusion Criteria

1. Age less than or equal to 21 years old at the time of study enrolment;
2. Diffuse Intrinsic Pontine Glioma (DIPG) diagnosed by MRI and/or histological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Diffuse Midline Glioma (DMG) with an H3K27M mutation or loss of H3K27 trimethylation;
3. Lansky / Karnofsky score greater than or equal to 50%;
4. Absolute lymphocyte count greater than or equal to 0.1×10^9/L;
5. No evidence of tumour progressionthe process by which a tumor grows and develops over time, becoming more aggressive and potentially spreading to other parts of the body following any form of anti-tumour treatment;
6. Life expectancy of greater than or equal to 12 weeks.

PART II Inclusion Criteria

1. 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 tumoura tissue mass that forms from groups of unhealthy cells;
2. 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 bloodthe red bodily fluid that transports oxygen and other nutrients around the body T cells (PBT);
3. 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;
4. Recovered to less than or equal to Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1 from the acutenew, recent, comes with an urgent or significant sense, is sudden, sharp toxic effects of all prior anti-cancer treatment at least a week before entering this study;
5. Life expectancy of greater than or equal to 6 weeks;
6. At least 4 weeks since major surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, and recovered adequately from the toxicity and/or complications from surgery;
7. 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;
8. Females of childbearing potential and fertile male patients must use an effective method of contraception starting with the first dosethe amount of medication taken of study therapy through 4 months after the last dose of study therapy;
9. For females of childbearing potential, the patient must have a negative serum pregnancy test at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening, and a negative urine pregnancy test, prior to dosing at each treatment course.