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)

Acute Lymphoblastic Leukemia Clinical Trial

— ALL  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04954326
• Other study ID #: CL2-95014-002
• Secondary ID: 2020-004894-29
• Status: Completed
• Phase: Phase 2
• Start date: May 7, 2021
• Est. completion date: May 20, 2022

Study information

• Verified date: July 2023
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: May 20, 2022
• Est. primary completion date: May 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Russian Federation	Regional Children Clinical Hospital	Chelyabinsk
Russian Federation	Regional Children Clinical Hospital	Ekaterinburg
Russian Federation	Children Regional Clinical Hospital	Krasnodar
Russian Federation	Russian Children Clinical Hospital	Moscow
Russian Federation	Regional Children Hospital	Nizhny Novgorod
Russian Federation	V.A. Almazov National Medical Research Center	Saint Petersburg

Sponsors (3)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company, Les Laboratoires Servier (L.L.S), Russia

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics Measurement	Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf)	Predose up to 600 hours
Primary	Pharmacokinetics Measurement	Maximum observed plasma asparaginase activity (Cmax)	Predose up to 600 hours
Secondary	Pharmacokinetics Measurements	Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014	14 days post-dose
Secondary	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
Secondary	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)

External Links

•   Find results on Servier Clinical Trial Data website