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

NCT ID: NCT03267030

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-23
• Study Completion Date: 2020-10-22

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GRASPA

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

Group Type: EXPERIMENTAL

GRASPA

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

Eryaspase

Eligibility Criteria

Inclusion Criteria

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

2. First line non-high risk ALL patients enrolled in NOPHO ALL2008 or ALLTogether pilot protocols including PEG-ASNase regimen.

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

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

4. Karnofsky/Lansky score ≥50.

5. 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.

Exclusion Criteria

1. Philadelphia chromosome positive ALL.

2. 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.

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;

1. History of pancreatitis

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

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

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

7. 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.

8. Patient under concomitant treatment likely to cause hemolysis.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ERYtech Pharma

INDUSTRY

Sponsor Role: collaborator

Birgitte Klug Albertsen

OTHER

Sponsor Role: lead

Responsible Party

Birgitte Klug Albertsen

MD PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Brigitte Klug Albertsen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Pediatric and adolescent medicine, Aarhus University Hospital, Denmark

Locations

Aahus University hospial, hematological department

Aarhus, Aarhus C, Denmark

Aarhus University hospital

Aarhus, Aarhus N, Denmark

Aalborg University Hospital, pediatric department

Aalborg, , Denmark

Rigshospitalet, Hematological department

Copenhagen, , Denmark

Rigshospitalet, Child and Adolescent Medicine

Copenhagen, , Denmark

Odense University hospital, pediatric department

Odense, , Denmark

Tallin Childrens Hospital

Tallinn, , Estonia

Tartu University Clinics

Tartu, , Estonia

Childrens Hospital, Helsinki. University Central Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

University Hospital of Oulu

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Vilnius University Children's Hospital

Vilnius, , Lithuania

Helse Bergen

Bergen, , Norway

Oslo Universitetssykehus, Rikshospitalet

Oslo, , Norway

St Olavs Hospital

Trondheim, , Norway

Drottning Silvias Barn- och ungdomssjukhus

Gothenburg, , 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

Countries

Denmark; Estonia; Finland; Lithuania; Norway; Sweden

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004451-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NOR-GRASPALL 2016

Identifier Type: -

Identifier Source: org_study_id