A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia

Phase 2

Completed

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Biological: SHP674

• Registration Number: NCT04067518
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

The objectives of the study are to assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1 and to assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-13
• Study First Submitted QC: 2019-08-22
• Study First Posted: 2019-08-26
• Study Start: 2019-10-17
• Primary Completion: 2021-02-12
• Study Completion: 2022-02-04
• Results First Submitted: 2022-05-13
• Results First Submitted QC: 2022-05-13
• Results First Posted: 2022-06-10
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-24
• Last Update Posted: 2023-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Age 1 to ≤21 years at the time of informed consent;
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2;
• Newly diagnosed, untreated precursor B-cell ALL
• No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent;
• Life expectancy of at least 6 months from the date of enrollment;

Read More

Exclusion Criteria

• Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL
• Preexisting known coagulopathy ;
• History of pancreatitis;
• Continuous use of corticosteroids;
• Prior treatment or possible prior treatment with an L-asparaginase preparation;
• History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs;
• Pregnant

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHP674	SHP674	Part 1: Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674 in the 36-week treatment period and who were stratified into the high risk (HR) group received total 8 doses of SHP674 in the 45-week treatment period. Part 2: Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674 in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674 in the 45-week treatment period.

Primary Outcome Measures

Name	Time	Method
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period	Up to 30 days after last dose of study drug (approximately 49 weeks)	An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.
Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674	14 days after the first dose of SHP674

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2)	Predose and 25 days post dose (Part 1 and part 2)
Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674	14 days after the first dose of SHP674
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL	Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose
Survival Rate at 1 Year After the Start of Study Treatment	1 year after the start of study treatment (from first dose up to 12 months)	Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment.
Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2)	Predose and 25 days post dose (Part 1 and Part 2)
Event-free Survival Rate at 1 Year After the Start of Study Treatment	1 year after the start of study treatment (from first dose up to 12 months)	Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment.

Trial Locations

Locations (8)

Kobe Children's Hospital Department of Hematology/Oncology; 🇯🇵 Kobe, Japan

Nagoya Medical Center Department of Pediatrics; 🇯🇵 Nagoya, Japan

Niigata Cancer Center Hospital; 🇯🇵 Niigata, Japan

Kagoshima University Hospital Department of Pediatrics; 🇯🇵 Kagoshima, Japan

Saitama Children's Medical Center Department of Hematology/Oncology; 🇯🇵 Saitama, Japan

Sapporo Hokuyu Hospital Department of Pediatrics and Adolescent Medicine; 🇯🇵 Sapporo, Japan

St. Luke's International Hospital Department of Pediatrics; 🇯🇵 Tokyo, Japan

National Cancer Center Hospital Department of Pediatric Oncology; 🇯🇵 Tokyo, Japan