Multi-modular Chimeric Antigen Receptor T cells tarGeting B7-H3 in children, Teenage & Young adult sarcoma (Rhabdomyosarcoma (RMS), Ewing’s Sarcoma (EWS) and Desmoplastic Small Round Cell Tumour (DSRCT))
Description
Design:
A multi-centre, open label, phase 1 trial using the continual reassessment method (CRM) to evaluate the safety and optimal biologic dose of dTBRII/hBRCA84D CAR T cells in patients with relapsed or refractory (r/r) Rhabdomyosarcoma (RMS), Ewing's Sarcoma (EWS) or Desmoplastic Small Round Cell Tumour (DSRCT).
Treatment:
- Leukapheresis: following registration, patients will undergo an unstimulated leukapheresis which will be sent to ‘Centre for Cell, Gene & Tissue Therapeutics’ (CCGTT) at the Royal Free Hospital for manufacture of the hBRCA84D CAR T cells
- Lymphodepletion: prior to hBRCA84D CAR T cell infusion patients will receive fludarabine 30 mg/m2 (on days -6 to -3) and cyclophosphamide 500 mg/m2 (on days -4 to-3).
- hBRCA84D CAR T cell infusion: Intravenous infusion of CAR T cells at a dose assigned to the patient by TMG/CTC according to the 3+3 design. The following dose levels will be tested:
- Dose Level 1: 30 x 106 CAR T cells/m2
- Dose Level 2: 100 x 106 CAR T cells/m2
Key inclusion/exclusion criteria:
Key inclusion criteria
- Age between 1 and 24 years
- Tissue diagnosis of Rhabdomyosarcoma, Ewing sarcoma or Desmoplastic small round cell tumour
- Relapsed or refractory disease after one or multiple lines of previous treatment
- Measurable disease by cross sectional imaging
- Absolute lymphocyte count ≥ 0.25 x 109/L
- Creatinine needs to be less than 1.5x if the upper limit of normality for age (if higher, an estimated (calculated) creatinine clearance must be more than ≥ 60 ml/min/1.73 m2)
Key exclusion criteria
- Patients with only bone marrow detectable disease (in the absence of measurable disease by imaging)
- Active, inoperative CNS disease including leptomeningeal disease
- Active HepB, HepC or HIV infection
Duration of recruitment:
Anticipated duration of recruitment is 2 years. This trial is not yet open to recruitment.
Aim
- To determine the feasibility of generating the ATIMP and administering the CAR T cells to patients with r/r RMS, EWS or DSRCT.
- To determine the safety and tolerability of the CAR T cells in patients with r/r RMS, EWS or DSRCT.