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.