L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
Status:
Terminated
Trial end date:
2018-03-01
Target enrollment:
Participant gender:
Summary
Asparaginase (Asp) is used during the induction phase of ALL treatment for children and young
adults. Its efficacy is counterbalanced by its toxicity, mainly in patients 40 years or
older. The efficacy rate in older adult population is lower than for children or young
adults. A recent review on outcomes in older adults with ALL pointed out that there were
significantly more drug reductions, omissions or delays in the older group as compared to
younger adults and that asparaginase was the drug most commonly omitted.
The investigational product ERYASPASE is a dispersion for infusion of homologous red blood
cells (RBC) encapsulating E. coli L-asparaginase.
A previous European phase I/II clinical study in children and adults (<55 yo) at first
relapse of ALL was conducted to determine the optimal dose of homologous RBC encapsulating
native E. coli Asp (GRASPA®) in 24 patients with relapsed ALL. The activity and safety
profiles of 3 doses of GRASPA® (50, 100 and 150 IU/kg) in combination with standard
chemotherapy were compared to free native Asp. The global safety profile is also improved,
reducing hypersensitivity, liver toxicity and coagulation disorders. Study showed that a
single dose of GRASPA® 150 IU/kg induced a depletion in plasmatic asparagine for 18.6 days,
i.e. similar to that obtained with 8 injections of 10,000 IU/m² of free native Asp. A
reduction in the incidence and severity of the allergic reactions and coagulation disorders
were observed with GRASPA® (Domenech 2011).
A French phase II study designed to determine the maximum tolerated dose of GRASPA® in
combination with a polychemotherapy regimen in ALL patients older than 55 yo at first
diagnosis has been performed, and showed that both 100 and 150 IU/kg doses fulfilled the
predefined criteria for efficacy and tolerability but the better profile of 100 IU/kg dose
was considered the optimal dose in this setting. A phase II/III trial in adult and children
patients with relapsed ALL is currently ongoing.
Based on these results, the combination of ERYASPASE with the CALGB chemotherapy regimen
appears to be an attractive combination for the treatment of adults patients with ALL/LBL.