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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Clinical Study of SHP674 in Patients With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: SHP674


Participation Criteria
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Eligibility Criteria
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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; 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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The intervention study model is sequential in results section of record.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP674<br>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. | Biological: SHP674<br>* SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m^2: 2500 IU/m^2 every 14 days if BSA <0.6 m^2: 82.5 IU/kg every 14 days<br>* Other names: Pegaspargase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | 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. | Up to 30 days after last dose of study drug (approximately 49 weeks) | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 | Survival rate is defined as the percentage of subjects who survived 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 at 1 Year After the Start of Study Treatment | 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. | 1 year after the start of study treatment (from first dose up to 12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoblastic Leukemia