Trial Details
Trial status:
Active (recruiting)
Recruitment start date:
Great Ormond Street Hospital Children's Charity (GOSHCC)
Chief Investigator:
Dr Karin Straathof
Recruitment target:
EudraCT number:
Contact details:
Lay summary:
Chimeric Antigen Receptor (CAR)-T cells to target GD2 for Diffuse Midline Glioma (DMG)
Design: A single centre, open label, phase 1 trial using the continual reassessment method (CRM) to evaluate the safety and optimal biologic dose of an Advanced Therapy Investigational Medicinal Product (ATIMP) in patients ages 2 to 16 years with Diffuse Midline Glioma (DMG). 
The ATIMP tested in this study is RQR8/huK28Z CAR T cells. 
A total of 12 patients will be treated at 1 participating site.
Patients will undergo an unstimulated leukapheresis which will be sent to CCGTT-RFH for manufacture of the RQR8/huK28Z CAR T cells. ATIMP manufacture takes about 15 days.
Patients will have an intracerebroventricular catheter (Ommaya catheter) placed following enrolment and prior to RQR8/huK28Z CAR T cell infusion to allow monitoring, and treatment (if necessary) of increased intracranial pressure (ICP) (both on theme 1 and 2) and if eligible, for intracerebroventricular infusion of RQR8/huK28Z CAR T cell administration (on theme 2).
Prior to the 1st IV CAR T cell infusion patients will receive fludarabine 30mg/m2 (on days -6 to -3) and cyclophosphamide 500mg/m2 (on days -4 to -3).

The RQR8/huK28Z CAR T cells will be given in two themes. All patients will receive treatment on Theme 1 (intravenous infusion) of CAR T cells at a dose assigned to the patient by TMG/CTC. 
The following dose levels will be tested:
• Dose Level 1: 30 x10^6 CAR T cells/m2
• Dose Level 2: 100 x10^6 CAR T cells/m2
• Dose Level 3: 300 x10^6 CAR T cells/m2

Patients whose disease does not respond to this intravenous infusion (or comes back (relapses) later) and in the absence of toxicity, may receive a second flat dose of 30x10^6 CAR T cells infusion in theme 2 (intracerebroventricular infusion delivered into the brain using Ommaya reservoir).

Patients will be followed up regularly until 1 year post-ATIMP infusion.  After 1 year, patients will continue to be followed up annually until 15 years post ATIMP infusion.
Key inclusion/exclusion criteria: Age between 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.
Patients with active HepB, HepC or HIV infection; with evidence of tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres are excluded from the study. Bilirubin needs to be less than than 1.5xULN, Creatinine to be less than than 1.5

Duration of recruitment: Anticipated duration of recruitment will be 2 years.
The aim of the study is to evaluate the safety, efficacy and optimal dose of RQR8/huK28Z CAR T cells in patients with DMG.

Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
Contact Us
Cancer Research UK & UCL Cancer Trials Centre
University College London
90 Tottenham Court Road

View map
+44 (0)20 7679 9898 (General CTC Enquiries)
020 7679 9899
University College London, Gower Street, London, WC1E 6BT +44 (0)20 7679 2000

Copyright © 2024 UCL | Disclaimer | Freedom of Information | Accessibility | Privacy | Cookies | Contact Us