Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma

Brief 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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Drug: L-asparaginase encapsulated in RBC Phase 1

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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
  • 50 IU/kg IV
  • 100 IU/kg IV
  • 150 IU/kg IV
  • 200 IU/kg IV
Other Name: ERYASPASE




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Overall safety and tolerability [ Time Frame: Duration of study ]
    Number, incidence, type, severity, outcome and causality of AE and SAE

  2. Plasma concentrations of asparagine,aspartate,glutamine and glutamate. [ Time Frame: Induction and consolidation phases ]
    Pharmacodynamic parameters (PD)

  3. Optional samples for CSF levels of amino acids [ Time Frame: Induction and consolidation phases ]
    PD parameters

  4. Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase [ Time Frame: Day of administration and 24h post administration ]
    Pharmacokinetic parameter

  5. Immunogenicity [ Time Frame: Duration of study ]
    Evaluation of the titer of the anti-asparaginase antibody


Other Outcome Measures:
  1. Response to treatment [ Time Frame: Induction and consolidation phases ]
    Hematological Complete Response rate



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women aged 18 years and over
  • Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma
  • Received no more than 1 prior treatment for ALL/LBL
  • Note: Patients who have received transplant during 1st remission are excluded since this would be considered a 2nd treatment
  • ECOG performance status 0-2
  • Signed Informed Consent Form

Exclusion Criteria:

  • Other serious medical illness other than that treated by this study which would limit survival to <2 years or psychiatric conditions which would prevent informed consent or compliance with treatment.
  • Presenting with a general or visceral contraindication to intensive treatment including:

    • uncontrolled or severe cardiovascular disease, including recent (<6 months) myocardial infarction or congestive heart failure,
    • Current Grade 3 or higher coagulopathy, thrombosis and/or hemostasis disorders,
    • Serum creatinine concentration, 1.5 times greater than the upper limit of laboratory normal ranges (ULN), except if related to ALL/LBL,
    • total bilirubin 1.5 times greater than the ULN, except if related to ALL/LBL,
    • transaminases (AST or ALT) levels, 5 times greater than the ULN, except if related to ALL/LBL,
    • An uncontrolled bacterial, viral, or fungal infection or an active duodenal ulcer, until these conditions are corrected or controlled.
  • History of Grade 3 or higher allergic reaction with prior asparaginase treatment,
  • History of allergy to penicillin or related antibiotic
  • History of Grade 3 or higher blood transfusion incident according to US Biovigilance Network which refers to any transfusion followed by a major intervention (vasopressors, intubation, transfer to intensive care) to prevent death.
  • Presenting with anti-erythrocyte antibodies leading to the unavailability of phenotype compatible red blood cells.
  • Participation in a clinical study involving receipt of an investigational drug during the last 30 days.
  • Women of childbearing potential without effective contraception as well as pregnant or breast feeding women.
  • Patient receiving treatment likely to cause hemolysis or under phenytoin treatment.
  • Patient undergoing yellow fever vaccination.

Information from the National Library of Medicine

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


Locations
Layout table for location information
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
Duke University
Durham, North Carolina, United States, 27705
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
ERYtech Pharma
Investigators
Layout table for investigator information
Principal Investigator: Richard A LARSON, MD University of Chicago
Layout table for additonal information
Responsible Party: ERYtech Pharma
ClinicalTrials.gov Identifier: NCT01910428    
Other Study ID Numbers: GRASPALL 2012-09
First Posted: July 29, 2013    Key Record Dates
Last Update Posted: July 5, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by ERYtech Pharma:
L-asparaginase encapsulated in RBCs, leukemia, lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Asparaginase
Antineoplastic Agents