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.