Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase
- Registration Number
- NCT03267030
- Lead Sponsor
- Birgitte Klug Albertsen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
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Male or female aged 1-45 years at diagnosis of ALL.
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First line non-high risk ALL patients enrolled in NOPHO ALL2008 or ALLTogether pilot protocols including PEG-ASNase regimen.
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Documented hypersensitivity reaction to PEG-ASNase with either:
Clinical allergy to PEG-ASNase (mild/severe). Serum ASNase activity below the lower level of quantification.
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Karnofsky/Lansky score ≥50.
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Ability to understand and willingness to sign a written ICF 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 had to provide consent.
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Philadelphia chromosome positive ALL.
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Participation in another clinical trial interfering with the study therapy with exception of NOPHO ALL-2008 or ALLTogether pilot protocol. Patients can participate in other clinical trials not interfering with the study drug. In case of doubt this is assessed by the PI.
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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.
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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.
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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).
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Inadequate organ functions, which prohibit further asparaginase administration;
- History of pancreatitis
- History of serious hemorrhage or serious thrombosis with prior asparaginase therapy
- Severe hepatic impairment at the time of administration (bilirubin >3 times ULN, transaminases >10 times ULN)
- Pre-existing known coagulopathy (e.g. haemophilia)
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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.
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Patient under concomitant treatment likely to cause hemolysis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GRASPA GRASPA GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity.
- Primary Outcome Measures
Name Time Method Pharmacokinetics ASNase Activity >100 U/L at 14 Days 14 days after first infusion The primary endpoint was the percentage of patients with ASNase activity \>100 U/L at 14 days following the first infusion (nadir). ASNase activity \>100 U/L is considered adequate for complete asparagine depletion in the blood.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic Parameters 14 days after fourth infusion Percentage of patients with ASNase activity \>100 U/L at 14 days following the fourth infusion of the 2-week dosing intervals. ASNase activity \>100 U/L is considered adequate for complete asparagine depletion in the blood.
Trial Locations
- Locations (23)
Tallin Childrens Hospital
🇪🇪Tallin, Estonia
Childrens Hospital, Helsinki. University Central Hospital
🇫🇮Helsinki, Finland
Tartu University Clinics
🇪🇪Tartu, Estonia
Turku University Hospital
🇫🇮Turku, Finland
Aarhus University hospital
🇩🇰Aarhus, Aarhus N, Denmark
Rigshospitalet, Hematological department
🇩🇰Copenhagen, Denmark
University Hospital of Oulu
🇫🇮Oulu, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Oslo Universitetssykehus, Rikshospitalet
🇳🇴Oslo, Norway
Aahus University hospial, hematological department
🇩🇰Aarhus, Aarhus C, Denmark
Aalborg University Hospital, pediatric department
🇩🇰Aalborg, Denmark
Odense University hospital, pediatric department
🇩🇰Odense, Denmark
Rigshospitalet, Child and Adolescent Medicine
🇩🇰Copenhagen, Denmark
Kuopio University Hospital
🇫🇮Kuopio, Finland
St Olavs Hospital
🇳🇴Trondheim, Norway
Vilnius University Children's Hospital
🇱🇹Vilnius, Lithuania
Helse Bergen
🇳🇴Bergen, Norway
Drottning Silvias Barn- och ungdomssjukhus
🇸🇪Göteborg, Sweden
Universitetssjukhuset Linköping
🇸🇪Linköping, Sweden
Skånes Universitets sjukhus
🇸🇪Lund, Sweden
Astrid Lindgrens Barnsjukhus Karolinska
🇸🇪Stockholm, Sweden
arn- och Ungdomscentrum Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Akademiska sjukhuset Uppsala
🇸🇪Uppsala, Sweden