Clincosm LogoSign in Get a demo

Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase

Sponsor
Birgitte Klug Albertsen (Other)
Overall Status
Completed
CT.gov ID
NCT03267030
Collaborator
ERYtech Pharma (Industry)
55
Enrollment
23
Locations
1
Arm
38
Actual Duration (Months)
2.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pegylated-asparaginase (PEG-ASP) is an important part of the treatment of childhood acute lymphoblastic leukaemia (ALL). Unfortunately 13% of patients develops allergy and further treatment is impossible. Furthermore, 6% of patients have developed antibodies (silent inactivation) and have no effect of the PEG-ASP treatment. Truncated asparaginase therapy is associated with inferior event-free survival outcomes, in particular relapse in central nervous system (CNS).

Eryaspase is a new formulation of asparaginase encapsulated in erythrocytes. The erythrocyte membrane protects asparaginase against fast degradation and elimination processes. The encapsulation eliminates the direct somatic contact, and it is hypothesized that this provides the potential to prolong the activity of the enzyme and reduce toxicities.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Single-Arm PharmacoKinetic/PharmacoDynamic and Safety Study of Eryaspase (GRASPA®) for Patients With Hypersensitivity to PEG-Asparaginase, Diagnosed With Ph(-) Acute Lymphoblastic Leukemia
Actual Study Start Date :
Aug 23, 2017
Actual Primary Completion Date :
Aug 1, 2020
Actual Study Completion Date :
Oct 22, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: GRASPA

GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity.

Drug: GRASPA
Administration of 1-7 doses of 150 IU/kg IV infusion. (every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses).
Other Names:
  • Eryaspase

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetic parameters [6 months]

      Enzyme activity (IU/L)

    2. Pharmacokinetic parameters [6 months]

      T1/2 (half-life time)

    3. Pharmacokinetic parameters [6 months]

      Area under the plasma concentration versus time curve (AUC)

    4. Pharmacokinetic parameters [6 months]

      Vss (Distribution Volume at steady state)

    5. Pharmacokinetic parameters [6 months]

      Mean Residence Time (MRT)

    6. Pharmacodynamic profile [6 months]

      Plasma concentrations of amino acids: asparagine, aspartate, glutamine, glutamate o Concentrations of amino acids in the cerebrospinal fluid (CSF): (asparagine, aspartate, glutamine, glutamate)

    7. Immunogenicity [6 months]

      Titers of anti-asparaginase antibodies and neutralizing antibodies

    Secondary Outcome Measures

    1. Incidence of hypersensitivity [6 months]

      allergic reactions (any grade) and silent inactivation

    2. Incidence of toxicity [6 months]

      Incidence of Treatment-emergent adverse events

    3. Interactions with maintenance therapy [6 months]

      Measurement of levels of maintenance metabolites from the maintenance

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Male or female aged 1-45 years at diagnosis of ALL

    2. First line non-high risk (HR) ALL patients enrolled in the treatment protocol Nordic Society of pediatric hematology and oncology (NOPHO) ALL 2008 including PEG-asparaginase regimen

    3. Documented hypersensitivity reaction to PEG-asparaginase with either:

    Clinical allergy to PEG-Asparaginase (mild/severe) OR Serum asparaginase activity below the lower level of quantification.

    1. Karnofsky/Lansky score ≥ 50.

    2. Ability to understand, and willingness to sign, a written informed consent document and to comply with the scheduled visits, treatment plans, laboratory tests, and other study procedures. For patients under 18 years of age, either both parents or the legally appointed representatives will need to provide consent.

    Exclusion Criteria:

    1. Philadelphia chromosome positive ALL.

    2. Participation in another clinical trial interfering with the study therapy with exception of NOPHO ALL-2008. Patients can participate in other clinical trials not interfering with the study drug. In case of doubt this is assessed by the PI.

    3. Uncontrolled intercurrent illness including, but not limited to, patients receiving combination antiretroviral therapy or patients with severe or systemic infection, or psychiatric illness/social situations that would limit compliance with study requirements.

    4. Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

    5. Pregnant or lactating females (serum human chorionic gonadotropin pregnancy test at screening). Use of a highly effective contraceptive measure in women of child-bearing potential and sexually active girls that are of child-bearing potential is required (contraceptive measures are specified in section 6.0).

    6. Inadequate organ functions, which prohibit further asparaginase administration;

    7. History of pancreatitis

    8. History of serious hemorrhage or serious thrombosis with prior asparaginase therapy

    9. Severe hepatic impairment at the time of administration (bilirubin >3 times ULN, transaminases >10 times ULN)

    10. Pre-existing known coagulopathy (e.g. haemophilia)

    11. History of grade 3 or higher transfusion reactions or any contraindication to receive blood transfusion. Presence of specific anti-erythrocytes antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient.

    12. Patient under concomitant treatment likely to cause hemolysis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aahus University hospial, hematological department Aarhus Aarhus C Denmark 8000
    2 Aarhus University hospital Aarhus Aarhus N Denmark 8200
    3 Aalborg University Hospital, pediatric department Aalborg Denmark
    4 Rigshospitalet, Hematological department Copenhagen Denmark 2100
    5 Rigshospitalet, Child and Adolescent Medicine Copenhagen Denmark
    6 Odense University hospital, pediatric department Odense Denmark
    7 Tallin Childrens Hospital Tallin Estonia
    8 Tartu University Clinics Tartu Estonia
    9 Childrens Hospital, Helsinki. University Central Hospital Helsinki Finland
    10 Kuopio University Hospital Kuopio Finland
    11 University Hospital of Oulu Oulu Finland
    12 Tampere University Hospital Tampere Finland
    13 Turku University Hospital Turku Finland
    14 Vilnius University Children's Hospital Vilnius Lithuania
    15 Helse Bergen Bergen Norway
    16 Oslo Universitetssykehus, Rikshospitalet Oslo Norway
    17 St Olavs Hospital Trondheim Norway
    18 Drottning Silvias Barn- och ungdomssjukhus Göteborg Sweden
    19 Universitetssjukhuset Linköping Linköping Sweden
    20 Skånes Universitets sjukhus Lund Sweden
    21 Astrid Lindgrens Barnsjukhus Karolinska Stockholm Sweden
    22 arn- och Ungdomscentrum Norrlands Universitetssjukhus Umeå Sweden
    23 Akademiska sjukhuset Uppsala Uppsala Sweden

    Sponsors and Collaborators

    • Birgitte Klug Albertsen
    • ERYtech Pharma

    Investigators

    • Principal Investigator: Brigitte Klug Albertsen, MD, PhD, Pediatric and adolescent medicine, Aarhus University Hospital, Denmark

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Birgitte Klug Albertsen, MD PhD, Aarhus University Hospital
    ClinicalTrials.gov Identifier:
    NCT03267030
    Other Study ID Numbers:
    • NOR-GRASPALL 2016
    • 2016-004451-70
    First Posted:
    Aug 30, 2017
    Last Update Posted:
    Jan 25, 2021
    Last Verified:
    Jan 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Birgitte Klug Albertsen, MD PhD, Aarhus University Hospital
    Hypersensitivity to PEG-asparaginase
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Hypersensitivity

    Study Results

    No Results Posted as of Jan 25, 2021