Acute Lymphoblastic LeukemiaPhase 2NCT03267030
Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase
A Phase 2 study testing GRASPA in people with Acute Lymphoblastic Leukemia, run by Birgitte Klug Albertsen at 23 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 45 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- GRASPA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 23 Aug 2017to 22 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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.
Trial locations and contacts
23 sites in 6 countries.
23 sites in 6 countries
Denmark6 sites
Aalborg University Hospital, pediatric department
Aalborg
Aahus University hospial, hematological department
Aarhus, Aarhus C, 8000
Aarhus University hospital
Aarhus, Aarhus N, 8200
Rigshospitalet, Hematological department
Copenhagen, 2100
Rigshospitalet, Child and Adolescent Medicine
Copenhagen
Odense University hospital, pediatric department
Odense
Sweden6 sites
Drottning Silvias Barn- och ungdomssjukhus
Gothenburg
Universitetssjukhuset Linköping
Linköping
Skånes Universitets sjukhus
Lund
Astrid Lindgrens Barnsjukhus Karolinska
Stockholm
arn- och Ungdomscentrum Norrlands Universitetssjukhus
Umeå
Akademiska sjukhuset Uppsala
Uppsala
Finland5 sites
Childrens Hospital, Helsinki. University Central Hospital
Helsinki
Kuopio University Hospital
Kuopio
University Hospital of Oulu
Oulu
Tampere University Hospital
Tampere
Turku University Hospital
Turku
Norway3 sites
Helse Bergen
Bergen
Oslo Universitetssykehus, Rikshospitalet
Oslo
St Olavs Hospital
Trondheim
Estonia2 sites
Tallin Childrens Hospital
Tallinn
Tartu University Clinics
Tartu
About this study
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
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
- Being tested
- GRASPA
- Keywords
- Hypersensitivity to PEG-asparaginase
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRASPADrug
Also called Eryaspase
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).
| Study group | Role | What they receive |
|---|---|---|
| GRASPA | Experimental | GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. Receives: Drug: GRASPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days after first infusion
Secondary outcomes (1)
Pharmacokinetic Parameters
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.
Measured: 14 days after fourth infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start23 Aug 2017
- Primary completion1 Aug 2020
- Study completion22 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Birgitte Klug Albertsen
- Sponsor type
- University, hospital or other
- Collaborators
- ERYtech Pharma
- Responsible party
- Sponsor-investigator, Birgitte Klug Albertsen, Aarhus University Hospital
- Investigators
- Brigitte Klug Albertsen, MD, PhD, Principal investigator, Pediatric and adolescent medicine, Aarhus University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03267030
- Sponsor's protocol ID
- NOR-GRASPALL 2016
- Other IDs
- 2016-004451-70, 2016
- Status last verified
- Aug 2023
- First submitted
- 2 May 2017
- Last updated
- 15 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03267030
- Acronym / sponsor ID
- NOR-GRASPALL 2016
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- Hypersensitivity to PEG-asparaginase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Birgitte Klug AlbertsenUniversity, hospital or other
- Collaborators
- ERYtech Pharma
- Study start
- 23 Aug 2017 (actual)
- Primary completion
- 1 Aug 2020 (actual)
- Study completion
- 22 Oct 2020 (actual)
- First posted
- 30 Aug 2017 (actual)
- Results
- Posted 15 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GRASPA | Experimental | Drug: GRASPAGRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. |
Who may qualify
- Ages
- 1 year to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRASPAAlso: EryaspaseAdministration 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). | Drug | GRASPA |
Primary outcome
Pharmacokinetics ASNase Activity >100 U/L at 14 Days
Time frame: 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.
1 secondary outcome
Pharmacokinetic Parameters
Time frame: 14 days after fourth infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Acute Lymphoblastic Leukemia
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitte Klug Albertsen, MD, PhD principal investigator
Pediatric and adolescent medicine, Aarhus University Hospital, Denmark
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GRASPA in people with Acute Lymphoblastic Leukemia, run by Birgitte Klug Albertsen at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Denmark, Sweden, Finland, Norway, Estonia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics ASNase Activity >100 U/L at 14 Days (time frame: 14 days after first infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.