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)

• ClinicalTrials.gov Identifier: NCT04954326
• Recruitment Status: Completed
• First Posted: July 8, 2021
• Last Update Posted: December 5, 2022
• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company; Les Laboratoires Servier (L.L.S), Russia
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia	Drug: Lyophilized S95014; Drug: Liquid S95014	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: May 7, 2021
• Actual Primary Completion Date: May 20, 2022
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics measurement [ Time Frame: Day 3 pre-dose just after the infusion,4h after the end of infusion; Day 4: 24h after the end of infusion; Day 5: 48h after the end of infusion; Day 8, Day 10, Day 12, Day 17, Day 21, Day 28 ]
   Area Under the Concentration-Time Curve (AUC)
2. Pharmacokinetics measurement [ Time Frame: Day 3 pre-dose just after the infusion,4h after the end of infusion; Day 4: 24h after the end of infusion; Day 5: 48h after the end of infusion; Day 8, Day 10, Day 12, Day 17, Day 21, Day 28 ]
   Maximum observed plasma asparaginase activity (Cmax)

Secondary Outcome Measures :

1. Pharmacokinetics measurements [ Time Frame: 14 days post-dose ]
   Additional PK parameters from the ones defined as primary endpoint (e.g. Ctrough at 14 days post-dose) will be assessed.
2. Activity measurement [ Time Frame: Day 10, Day 17, Day 21 and Day 28 of induction ]
   Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration of either liquid or lyophilized S95014.
3. Immunogenicity measurements [ Time Frame: Day 3 pre-dose, Day 17 and Day 28 ]
   Anti S95014 and anti-PEG antibodies will be assessed for both lyophilized and liquid S95014 formulations.
4. Incidence of Treatment Emergent Adverse Events (safety and tolerability assessments) [ Time Frame: Through study completion, an average of 1 year ]
   Treatment Emergent Adverse Events (TEAEs) causality and severity based on NCI CTCAE 5.0.
5. Incidence of Serious Adverse Event (safety assessments) [ Time Frame: Through study completion, an average of 1 year ]
   Serious Adverse Event (SAEs) causality and severity based on NCI CTCAE 5.0.

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Russian Federation

Regional Children Clinical Hospital

Chelyabinsk, Russian Federation, 454087

Regional Children Clinical Hospital

Ekaterinburg, Russian Federation, 620149

Children Regional Clinical Hospital

Krasnodar, Russian Federation, 350007

Russian Children Clinical Hospital

Moscow, Russian Federation, 119571

Regional Children Hospital

Nizhny Novgorod, Russian Federation, 603136

V.A. Almazov National Medical Research Center

Saint Petersburg, Russian Federation, 197341

Sponsors and Collaborators

Institut de Recherches Internationales Servier

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.

More Information

Additional Information:

Find results on Servier Clinical Trial Data website 

Study Data/Documents: Individual Participant Data Set 

Study Protocol 

Statistical Analysis Plan 

Informed Consent Form 

Clinical Study Report 

Study-level clinical trial data 

• Responsible Party: Institut de Recherches Internationales Servier
• ClinicalTrials.gov Identifier: NCT04954326
• Other Study ID Numbers: CL2-95014-002; 2020-004894-29 ( EudraCT Number )
• First Posted: July 8, 2021
• Last Update Posted: December 5, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• 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.
• URL: https://clinicaltrials.servier.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Servier ( Institut de Recherches Internationales Servier ):

Oncology / Haematology; Phase II; Acute Lymphoblastic Leukemia; Parallel group; Pegaspargase; Pharmacokinetics comparability; Lyophilized pegaspargase; Liquid pegaspargase; Pegaspargase formulation; Randomized, open-label

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases