Phase 1
The first trials to determine the safety and feasibility of tisagenlecleucel (produced at that time at the University of Pennsylvania as CTL019) in B-ALL were phase 1/2a single arm, single center, open label studies [clinicaltrials.gov NCT01626495 and NCT01029366] conducted at the Children’s Hospital of Philadelphia (CHOP) 18 and the University of Pennsylvania (U Penn). In 2014, 30 patients (25 children, 5 adults) with relapsed or refractory CD19+ B-ALL were reported from these two trials 19; 18 patients had previously undergone allogeneic HSCT. The overall response rate, defined as either CR or CRi, was 90% one-month post-infusion. Nineteen patients (63%) demonstrated continued remission at time of publication with a median follow up time of 7 months (range 1-24 months).
Updated results focused on the pediatric cohort (n=59) presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2016 demonstrated 55 patients (93%) were in complete remission at one-month post-infusion with negative MRD in 52 patients (88%). Relapse-free survival (RFS) was 76% at 6 months and 55% at 12 months, and overall survival was 79% at 12 months. Twenty patients subsequently relapsed with the majority (13) demonstrating antigen escape with a CD19-negative phenotype. CTL019 persistence was accompanied by B cell aplasia, which continued up to last assessment (1-39 months) in 24 of 34 patients with ongoing CR 20, showing that B cell aplasia could be used as a widely available pharmacodynamic marker for functional CAR T persistence. The first patient treated on that trial remains in continuous CR without further therapy at 8 years.