Trial Outcomes & Findings for Asparaginase Encapsulated in Erythrocytes for Patients With ALL and Hypersensitivity to PEG-asparaginase (NCT NCT03267030)

Last Updated: 2024-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

14 days after first infusion

Results posted on

2024-03-15

Participant Flow

Participant milestones

Participant milestones
Measure	GRASPA GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008 (NCT: NCT00819351), eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol (NCT: NCT03911128) eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Overall Study STARTED	55
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GRASPA n=55 Participants GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008, eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Age, Categorical <=18 years	53 Participants n=55 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=55 Participants
Age, Categorical >=65 years	0 Participants n=55 Participants
Age, Continuous	6.1 years n=55 Participants
Sex: Female, Male Female	17 Participants n=55 Participants
Sex: Female, Male Male	38 Participants n=55 Participants
Region of Enrollment Sweden	15 Participants n=55 Participants
Region of Enrollment Norway	5 Participants n=55 Participants
Region of Enrollment Finland	8 Participants n=55 Participants
Region of Enrollment Denmark	10 Participants n=55 Participants
Region of Enrollment Lithuania	14 Participants n=55 Participants
Region of Enrollment Estonia	3 Participants n=55 Participants

PRIMARY outcome

Timeframe: 14 days after first infusion

Population: The primary Evaluable Patients (EP) Population was used for the analysis of the primary and key secondary endpoints, defined as all patients recruited into the study who provided data on ASNase level on Day 14 (±2 days) following the first administration of eryaspase. All included patients (55) completed first infusion, only in 53 patients an ASNase activity measurement was available.

Outcome measures

Outcome measures
Measure	GRASPA n=53 Participants GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008, eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Pharmacokinetics ASNase Activity >100 U/L at 14 Days	92.5 percentage of patients

SECONDARY outcome

Timeframe: 14 days after fourth infusion

Population: A total of 12 patients completed 4 infusions with a 2-week interval of these 9 patients had an ASNase activity measurement 14 days following the 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.

Outcome measures

Outcome measures
Measure	GRASPA n=9 Participants GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008, eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Pharmacokinetic Parameters	66.7 percentage of patients

Adverse Events

Intervention

Serious events: 6 serious events

Other events: 18 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Intervention n=55 participants at risk GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008, eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Hepatobiliary disorders hepatotoxicity	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Immune system disorders Haemophagocytic lymphohistiocytosis	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Immune system disorders Hypersenditivity	3.6% 2/55 • Number of events 2 • From first study drug administration and until 30 days after last administration, up to 1 year
Infections and infestations Device related infection	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Nervous system disorders Leukoencephalopathy	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year

Other adverse events

Other adverse events
Measure	Intervention n=55 participants at risk GRASPA will replace remaining PEG-asparaginase doses in case of hypersensitivity. GRASPA: Administration of 1-7 doses of 150 U/kg IV infusion. (For patients coming from NOPHO 2008, eryaspase was administered every 2 weeks for a maximum of 4 doses and every 6 weeks for maximum 3 doses, for patients in the ALLTogether pilot protocol eryaspase was administered at a dose of 150 U/kg every 2 weeks for a maximum of 7 doses).
Gastrointestinal disorders Constipation	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
General disorders Pyrexia	9.1% 5/55 • Number of events 9 • From first study drug administration and until 30 days after last administration, up to 1 year
Skin and subcutaneous tissue disorders urticaria	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Investigations Alanine aminotransferase increase	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Metabolism and nutrition disorders hyperlipidemia	3.6% 2/55 • Number of events 2 • From first study drug administration and until 30 days after last administration, up to 1 year
Musculoskeletal and connective tissue disorders Bone pain	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Investigations Weight decreased	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Infections and infestations Device related infection	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Immune system disorders Hypersensibility	5.5% 3/55 • Number of events 4 • From first study drug administration and until 30 days after last administration, up to 1 year
Infections and infestations Pneumonia	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
General disorders Febrile Neutropenia	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Skin and subcutaneous tissue disorders Rash	3.6% 2/55 • Number of events 2 • From first study drug administration and until 30 days after last administration, up to 1 year
Infections and infestations Herpes zoster	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Musculoskeletal and connective tissue disorders Osteonecrosis	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Gastrointestinal disorders Stomatitis	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Gastrointestinal disorders Nausea	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Infections and infestations Infection	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
General disorders hyperthermia	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year
Skin and subcutaneous tissue disorders rash pruritic	1.8% 1/55 • Number of events 1 • From first study drug administration and until 30 days after last administration, up to 1 year

Additional Information

Dr Birgitte Klug Albertsen

NOPHO

Phone: +45 20224643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place