New Medicines

Acute lymphoblastic leukaemia (ALL) in children


New molecular entity

Development and Regulatory status

Phase I Clinical Trials


A next generation autologous anti-CD22 and anti-CD19 chimeric antigen receptor-T (CAR-T) cell therapy. Inclusion of the CD22 CAR is designed to reduce antigen negative relapse of disease.
Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years. ALL represents 12% of all leukaemia (but 80% in children) [1].
Acute lymphoblastic leukaemia (ALL) in children

Trial or other data

Mar 21Autolus reported that it started a PI trial in pediatric patients with relapsed or refractory ALL with its next-generation product candidate, AUTO1/22 in Q4 20. It expects to report initial data from this trial in Q4 21 [6].
Mar 21In the PI CARPALL trial, enrolment completed with AUTO-1 (obecabtagene autoleucel). However, the extension arm is now open, and treating pediatric ALL patients with AUTO 1/22 (previously designated AUTO1NG). As of the data cut-off date of November 22, 2019, the trial has enrolled a total of 25 patients, in two cohorts; one cohort utilized a manual manufacturing process (cohort 1) and one cohort utilized a semi-automated fully enclosed manufacturing process (cohort 2). Product was generated for 14 of 17 patients in cohort 1 and the median follow-up for the 14 treated patients was 23 months. Seven patients were treated in cohort 2. The aim of cohort 2 was to increase feasibility of manufacture at scale; one patient died before infusion and product was generated for 100% of patients. Median follow-up for patients in cohort 2 was seven months [6].
Nov 20PI CARPALL trial is active but has finished recruitment [2].
Nov 19Results announced from PI CARPALL trial. 19 out of 21 treated patients (90%) achieved molecular complete remission at one month post infusion. CAR T cell expansion was excellent and was detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at one month post infusion. In the 14 patients in cohort 1, the overall survival at six months was 86% and at 12 months was 71%; event free survival at six months was 71% and at 12 months was 54%. The patients in cohort 2 were not evaluable for these parameters. Overall, eight patients relapsed; five of eight evaluable relapses were due to loss of CD19 antigen on the tumor cells [3,4].
Apr 16PI CARPALL trial to evaluate the safety, efficacy and duration of response of AUTO1 in children and young adults with CD19+ haematological malignancies, including ALL (precursor cell lymphoblastic leukaemia lymphoma) and Burkitt lymphoma starts (UCL 14/0529; NCT02443831). 32 patients aged up to 24 years will be recruited in the UK (at Great Ormond Street Hospital, University College Hospital in London, Royal Manchester Infirmary, and Royal Manchester Royal Children´s Hospital). Primary outcomes are toxicity and molecular remission; collection of these data are due to complete Nov 19 [2].