L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL

Acute Lymphoblastic Leukemia Clinical Trial

Official title: A Phase I Study of L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) in Combination With the CALGB Regimen During Induction and Consolidation Phases in the Treatment of Adult Patients With Acute Lymphoblastic Leukemia and Lymphoma

Status Terminated

Clinical Trial 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.

Clinical Trial Description

A phase I study to assess the limiting toxicities, global safety and clinical activity of ERYASPASE, using a dose titration design to confirm that the safety profile of ERYASPASE in combination with the CALGB chemotherapy regimen is similar to that observed in the European chemotherapy regimen. PK/PD and immunogenicity parameters will also be evaluated. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Lymphoma
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT01910428
• Study type: Interventional
• Source: ERYtech Pharma
• Status: Terminated
• Phase: Phase 1
• Start date: October 2013
• Completion date: March 2018