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) (ALL)

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)

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

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Lyophilized S95014; Drug: Liquid S95014

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Regional Children Clinical Hospital
  • Ekaterinburg, Russian Federation, 620149
    • Regional Children Clinical Hospital
  • Krasnodar, Russian Federation, 350007
    • Children Regional Clinical Hospital
  • Moscow, Russian Federation, 119571
    • Russian Children Clinical Hospital
  • Nizhny Novgorod, Russian Federation, 603136
    • Regional Children Hospital
  • Saint Petersburg, Russian Federation, 197341
    • V.A. Almazov National Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S95014 lyophilizate; 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; 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.
Active Comparator: S95014 liquid; 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; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company; Les Laboratoires Servier (L.L.S), Russia
• Investigators: Principal Investigator: Alexander Isaakovich Karachunskiy, PhD, Director of Institute of Oncology, Radiology and Nuclear Medicine. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Publications and helpful links

Helpful Links

• Find results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Actual): May 20, 2022
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: June 18, 2021
• First Submitted That Met QC Criteria: June 29, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia; Phase II; Oncology / Haematology; Pegaspargase; Lyophilized pegaspargase; Parallel group; Pharmacokinetics comparability; Liquid pegaspargase; Pegaspargase formulation; Randomized, open-label
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: CL2-95014-002; 2020-004894-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No