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

NCT03267030 | Completed Phase 2 Results DMC

• 2 other identifiers: NOR-GRASPALL 20162016-004451-70
• Study Type: interventional
• Target: 55
• Locations: 6 countries
• Sites: 23

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

Keywords

Hypersensitivity to PEG-asparaginase

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics ASNase Activity >100 U/L at 14 Days

  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.

  14 days after first infusion

Secondary Outcomes (1)

• Pharmacokinetic Parameters

  14 days after fourth infusion

Study Arms (1)

GRASPA

EXPERIMENTAL

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

Drug: GRASPA

Interventions

GRASPA 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).

Also known as: Eryaspase

GRASPA

Eligibility Criteria

• Age: 1 Year - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female aged 1-45 years at diagnosis of ALL.
• First line non-high risk ALL patients enrolled in NOPHO ALL2008 or ALLTogether pilot protocols including PEG-ASNase regimen.
• Documented hypersensitivity reaction to PEG-ASNase with either:
• Clinical allergy to PEG-ASNase (mild/severe). Serum ASNase activity below the lower level of quantification.
• Karnofsky/Lansky score ≥50.
• 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.

You may not qualify if:

• Philadelphia chromosome positive ALL.
• 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.
• 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.
• 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.
• 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).
• 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)
• 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.
• Patient under concomitant treatment likely to cause hemolysis.

Sponsors & Collaborators

• Birgitte Klug Albertsen: lead
• ERYtech Pharma: collaborator

Study Sites (23)

Aahus University hospial, hematological department

Aarhus, Aarhus C, 8000, Denmark

Location

Aarhus University hospital

Aarhus, Aarhus N, 8200, Denmark

Location

Aalborg University Hospital, pediatric department

Aalborg, Denmark

Location

Rigshospitalet, Hematological department

Copenhagen, 2100, Denmark

Location

Rigshospitalet, Child and Adolescent Medicine

Copenhagen, Denmark

Location

Odense University hospital, pediatric department

Odense, Denmark

Location

Tallin Childrens Hospital

Tallinn, Estonia

Location

Tartu University Clinics

Tartu, Estonia

Location

Childrens Hospital, Helsinki. University Central Hospital

Helsinki, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

University Hospital of Oulu

Oulu, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turku University Hospital

Turku, Finland

Location

Vilnius University Children's Hospital

Vilnius, Lithuania

Location

Helse Bergen

Bergen, Norway

Location

Oslo Universitetssykehus, Rikshospitalet

Oslo, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

Drottning Silvias Barn- och ungdomssjukhus

Gothenburg, Sweden

Location

Universitetssjukhuset Linköping

Linköping, Sweden

Location

Skånes Universitets sjukhus

Lund, Sweden

Location

Astrid Lindgrens Barnsjukhus Karolinska

Stockholm, Sweden

Location

arn- och Ungdomscentrum Norrlands Universitetssjukhus

Umeå, Sweden

Location

Akademiska sjukhuset Uppsala

Uppsala, Sweden

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

eryaspase

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr Birgitte Klug Albertsen
• Organization: NOPHO

biralber@rm.dk

+45 20224643

Study Officials

• Brigitte Klug Albertsen, MD, PhD

  Pediatric and adolescent medicine, Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: August 30, 2017
• Study Start: August 23, 2017
• Primary Completion: August 1, 2020
• Study Completion: October 22, 2020
• Last Updated: March 15, 2024
• Results First Posted: March 15, 2024

Record last verified: 2023-08

Locations

ES (2); FI (5); LI (1); DK (6); NO (3); SE (6)