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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)

Primary Purpose

Acute Lymphoblastic Leukemia

Status

Completed

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Lyophilized S95014

Liquid S95014

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Oncology / Haematology, Phase II, Acute Lymphoblastic Leukemia, Parallel group, Pegaspargase, Pharmacokinetics comparability, Lyophilized pegaspargase, Liquid pegaspargase, Pegaspargase formulation, Randomized, open-label

Eligibility Criteria

1 Year - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Regional Children Clinical Hospital
Regional Children Clinical Hospital
Children Regional Clinical Hospital
Russian Children Clinical Hospital
Regional Children Hospital
V.A. Almazov National Medical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

S95014 lyophilizate

S95014 liquid

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Pharmacokinetics Measurement

Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf)

Pharmacokinetics Measurement

Maximum observed plasma asparaginase activity (Cmax)

Secondary Outcome Measures

Pharmacokinetics Measurements

Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014

Activity Measurement

Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration 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).

Full Information

NCT ID

NCT04954326

First Posted

June 18, 2021

Last Updated

July 10, 2023

Sponsor

Institut de Recherches Internationales Servier

Collaborators

ADIR, a Servier Group company, Les Laboratoires Servier (L.L.S), Russia

1. Study Identification

Unique Protocol Identification Number

NCT04954326

Brief Title

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)

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

May 7, 2021 (Actual)

Primary Completion Date

May 20, 2022 (Actual)

Study Completion Date

May 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut de Recherches Internationales Servier

Collaborators

ADIR, a Servier Group company, Les Laboratoires Servier (L.L.S), Russia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

89 (Actual)

8. Arms, Groups, and Interventions

Arm Title

S95014 lyophilizate

Arm Type

Experimental

Arm Description

Arm Title

S95014 liquid

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Lyophilized S95014

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Liquid S95014

Intervention Description

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.

Primary Outcome Measure Information:

Title

Pharmacokinetics Measurement

Description

Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf)

Time Frame

Predose up to 600 hours

Title

Pharmacokinetics Measurement

Description

Maximum observed plasma asparaginase activity (Cmax)

Time Frame

Predose up to 600 hours

Secondary Outcome Measure Information:

Title

Pharmacokinetics Measurements

Description

Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014

Time Frame

14 days post-dose

Title

Activity Measurement

Description

Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration of either liquid or lyophilized S95014.

Time Frame

Day 7, 14, 18 and 25 post-dose of either liquid or lyophilized S95014

Title

Immunogenicity Measurements

Description

Anti-drug antibodies (ADA) formation against S95014 and anti-PEG with the lyophilized or liquid formulations (positive patients).

Time Frame

Pre-dose, post-dose (sum of 14 and 25 days post-dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexander Isaakovich Karachunskiy, PhD

Organizational Affiliation

Director of Institute of Oncology, Radiology and Nuclear Medicine. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Official's Role

Principal Investigator

Facility Information:

Facility Name

Regional Children Clinical Hospital

City

Chelyabinsk

ZIP/Postal Code

454087

Country

Russian Federation

Facility Name

Regional Children Clinical Hospital

City

Ekaterinburg

ZIP/Postal Code

620149

Country

Russian Federation

Facility Name

Children Regional Clinical Hospital

City

Krasnodar

ZIP/Postal Code

350007

Country

Russian Federation

Facility Name

Russian Children Clinical Hospital

City

Moscow

ZIP/Postal Code

119571

Country

Russian Federation

Facility Name

Regional Children Hospital

City

Nizhny Novgorod

ZIP/Postal Code

603136

Country

Russian Federation

Facility Name

V.A. Almazov National Medical Research Center

City

Saint Petersburg

ZIP/Postal Code

197341

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://clinicaltrials.servier.com/

Links:

URL

https://clinicaltrials.servier.com

Description

Find results on Servier Clinical Trial Data website

Available IPD and Supporting Information:

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://clinicaltrials.servier.com

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://clinicaltrials.servier.com

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://clinicaltrials.servier.com

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://clinicaltrials.servier.com

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://clinicaltrials.servier.com

Available IPD/Information Type

Study-level clinical trial data

Available IPD/Information URL

https://clinicaltrials.servier.com

Learn more about this trial

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)

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