L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
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|ClinicalTrials.gov Identifier: NCT01910428|
Recruitment Status : Terminated (Sponsor decision based off site/PI feedback about)
First Posted : July 29, 2013
Last Update Posted : July 5, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma||Drug: L-asparaginase encapsulated in RBC||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 2013|
|Actual Primary Completion Date :||January 25, 2018|
|Actual Study Completion Date :||March 2018|
Experimental: L-asparaginase encapsulated in RBC
L-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg
Drug: L-asparaginase encapsulated in RBC
Other Name: ERYASPASE
- Determination of the Maximal Total Dosage (MTD) based on number of patients presenting with related DLT [ Time Frame: Duration of study ]ERYASPASE administered during the induction and consolidation phases of the standard multi-agent CALBG chemotherapy
- Overall safety and tolerability [ Time Frame: Duration of study ]Number, incidence, type, severity, outcome and causality of AE and SAE
- Plasma concentrations of asparagine,aspartate,glutamine and glutamate. [ Time Frame: Induction and consolidation phases ]Pharmacodynamic parameters (PD)
- Optional samples for CSF levels of amino acids [ Time Frame: Induction and consolidation phases ]PD parameters
- Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase [ Time Frame: Day of administration and 24h post administration ]Pharmacokinetic parameter
- Immunogenicity [ Time Frame: Duration of study ]Evaluation of the titer of the anti-asparaginase antibody
- Response to treatment [ Time Frame: Induction and consolidation phases ]Hematological Complete Response rate
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01910428
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|University of Maryland, Greenebaum Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, New York|
|Monter Cancer Center|
|Lake Success, New York, United States, 11042|
|United States, North Carolina|
|Durham, North Carolina, United States, 27705|
|United States, Ohio|
|Ohio State University|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Richard A LARSON, MD||University of Chicago|