A Study Comparing the Blood Levels of Both Pegaspargase (S95014) Formulations (Liquid vs Lyophilized) in the Treatment of Paediatric Patients With Acute Lymphoblastic Leukemia (ALL)

Study Overview
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Brief Summary
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The purpose of this study is to compare the pharmacokinetics (PK) of both lyophilized and liquid S95014 formulations during the induction phase after a single IV dose in newly diagnosed paediatric patients with ALL

Official Title
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A Multicentre, Phase II Randomized Study, Open-label, With 2-arm Parallel Group, Comparing the Pharmacokinetics of the Liquid and the Lyophilized Formulations of Pegaspargase (S95014) in Treatment of Paediatric Patients With Newly-Diagnosed Acute Lymphoblastic Leukemia (ALL)

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Lyophilized S95014
* Drug: Liquid S95014


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 1 to < 18 years Patients with cytologically confirmed and documented newly diagnosed ALL according to National Comprehensive Cancer Network guidelines 2020 (see Appendix 2), excluding B-cell Burkitt ALL Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 (see Appendix 3) Highly effective contraception method Signed informed consent and assent, when appropriate Non-inclusion Criteria: Unlikely to cooperate in the study Pregnant and lactating women Participation in another interventional study at the same time; participation in non-interventional registries or epidemiological studies is allowed Participant already enrolled in the study (informed consent signed) Women of childbearing potential tested positive in a serum pregnancy test within 7 days prior to the treatment period Inadequate hepatic function (bilirubin > 1.5 times upper limit of normal (ULN), transaminases > 5x ULN) Inadequate renal function defined as serum creatinine > 1.5 x ULN Prior treatment with chemotherapy or radiotherapy (except steroids and intrathecal therapy) Prior surgery or bone marrow transplant related to the studied disease Down Syndrome Psychiatric illness/social situation that would limit compliance with study requirements Known history of pancreatitis Known history of significant liver disease Known carriers of HIV antibodies Significant laboratory abnormality likely to jeopardize the patients' safety or to interfere with the conduct of the study, in the investigator's opinion Pre-existing known coagulopathy (e.g. haemophilia and known protein S deficiency) History of previous or concurrent malignancy History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs Severe or uncontrolled active acute or chronic infection Uncontrolled intercurrent illness including life-threatening acute tumor lysis syndrome (e.g. with renal failure), symptomatic congestive heart failure, cardiac arrhythmia

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S95014 lyophilizate<br>Lyophilized S95014 reconstituted will provide 5 mL of extractable volume with the concentration of 750 U/mL. The vial of lyophilized powder (3.750 U/vial) is reconstituted with 5.2 mL of Sterile Water for Injection to obtain a 750 U/mL solution for single use. | Drug: Lyophilized S95014<br>* Lyophilized S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol.<br>|
| Active Comparator: S95014 liquid<br>Liquid S95014 is provided as 3.750 U per 5 mL solution in a single use vial to obtain a 750 U/mL solution for single use. | Drug: Liquid S95014<br>* Liquid S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Measurement | Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf) | Predose up to 600 hours | 
| Pharmacokinetics Measurement | Maximum observed plasma asparaginase activity (Cmax) | Predose up to 600 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Measurements | Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014 | 14 days post-dose | 
| Activity Measurement | Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration of either liquid or lyophilized S95014. | Day 7, 14, 18 and 25 post-dose of either liquid or lyophilized S95014 | 
| Immunogenicity Measurements | Anti-drug antibodies (ADA) formation against S95014 and anti-PEG with the lyophilized or liquid formulations (positive patients). | Pre-dose, post-dose (sum of 14 and 25 days post-dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology / Haematology, Phase II, Acute Lymphoblastic Leukemia, Parallel group, Pegaspargase, Pharmacokinetics comparability, Lyophilized pegaspargase, Liquid pegaspargase, Pegaspargase formulation, Randomized, open-label