MIGHTY is a multicentre, open label, phase 1 clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children, teenagers and young adults aged 1-24 with relapsed or refractory (r/r) rhabdomyosarcoma (RMS), Ewing sarcoma (ES) or desmoplastic small round cell tumour (DSRCT). The study will assess the feasibility of generating the ATIMP and administering hBRCA84D CAR T cells to patients with r/r RMS, ES or DSRCT.
MIGHTY is a multicentre, open label, phase 1 clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children, teenagers and young adults aged 1-24 with relapsed or refractory (r/r) rhabdomyosarcoma (RMS), Ewing sarcoma (ES) or desmoplastic small round cell tumour (DSRCT). The ATIMP for this study (hBRCA84D CAR T cells) are autologous T cells targeting B7-H3 in patients with r/r RMS, ES, or DSRCT. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. Patients will receive lymphodepleting (LD) chemotherapy with fludarabine administered over 4 days (Day -6 to Day -3) and cyclophosphamide administered over 2 days (Day -4 and Day-3). Patients will be treated at one of three dose levels following LD chemotherapy as described above. The study will evaluate the feasibility of generating the ATIMP, the safety of administering ATIMP, the tolerability of the ATIMP and how effectively the CAR T cells engraft, expand and persist following administration in patients with r/r RMS, ES or DSRCT. Following infusion of the CAR T cells, patients will be monitored for between 2-4 weeks as an inpatient. Following discharge, patients will enter the interventional follow up phase and be followed up for 1 year. Patients will be seen at 6 weeks post infusion then 3 monthly until 1 year post CAR T cells infusion. If patients relapse within the first-year post CAR T cell infusion, they will come off the interventional follow up and will be followed up annually until 15 years after the CAR T infusion. After completing the 1-year interventional phase of the study, all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 15 years post CAR T infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
The hBRCA84D CAR T cells target B7-H3 positive cells.
Great Ormond Street Hospital
London, United Kingdom
RECRUITINGUniversity College London Hospital
London, United Kingdom
RECRUITINGSafety of administering the ATIMP
Incidence of grade 3-5 toxicity causally related to the ATIMP, particularly severe cytokine release syndrome and severe neurotoxicity.
Time frame: 28 days
Number of therapeutic products generated and the number of ATIMPs infused after successful manufacture
Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture.
Time frame: 28 days
Objective response rate
Based on cross-sectional imaging after the ATIMP intravenous administration
Time frame: 1 year
Progression Free Survival (PFS)
Progression Free Survival (PFS) after the ATIMP intravenous administration
Time frame: 1 year
Time to Progression (TTP)
Time to Progression (TTP) after the ATIMP intravenous administration
Time frame: 1 year
Overall survival
Overall Survival after the ATIMP intravenous administration
Time frame: 1 year
Karin Straathof
CONTACT
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Masking
NONE
Enrollment
12