Clinical Trial Results:
A multicentre, roll-over study to provide continued treatment with lyophilized pegaspargase (S95014) in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL)
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Summary
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EudraCT number |
2020-004895-17 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
23 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jul 2023
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First version publication date |
26 Jul 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CL2-95014-003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04956666 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Investigational New Drug Application No.: 152743 | ||
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Sponsors
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Sponsor organisation name |
Institut de Recherches Internationales Servier and Les Laboratoires Servier (L.L.S.)
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Sponsor organisation address |
50 rue Carnot, Suresnes Cedex, France, 92284
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Public contact |
Clinical Studies Department, Institut de Recherches Internationales Servier, +33 155724366, clinicaltrials@servier.com
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Scientific contact |
Clinical Studies Department, Institut de Recherches Internationales Servier, +33 155724366, clinicaltrials@servier.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Apr 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Jan 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jan 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To provide treatment with lyophilized S95014 in pediatric patients with ALL who completed the CL2-95014-002 study during the induction phase.
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Protection of trial subjects |
The study was performed in accordance with the ethical principles stated in the Declaration of Helsinki 1964, as revised in Fortaleza, 2013 with the good clinical practice (GCP) and with the applicable regulatory requirements.
Each patient, in the presence of their parent(s) / legal guardians, was informed by the investigator (or their delegate) to the fullest extent possible about the details of the study in language and terms they could understand. The patients were also informed that they had the possibility not to participate in the study and that they were free to reconsider their assent at any time.
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Background therapy |
The following treatments were to be used with caution during the whole treatment phase: - Coumarin/warfarin and heparin, dipyridamole, acetylsalicylic acid or non-steroidal anti-inflammatory medicines (e.g. ibuprofen, naproxen) - Prednisone, methotrexate, vincristine, cytarabine. The main pharmacological classes of concomitant treatments, listed by decreasing frequency of use, were: - 70% or more patients: antiemetics and antinauseants, antibacterials for systemic use, blood substitutes and perfusion solutions. - 60% to 70% of patients: corticosteroids for systemic use, antihistamines for systemic use, antithrombotic agents. - 40% to 60% of patients: drugs for acid related disorders, mineral supplements, bile and liver therapy, antimycotics for systemic use, antianemic preparations. - 20% to 40% of patients: antivirals for systemic use, analgesics, digestives, incl. enzymes, antihemorrhagics, psychoanaleptics, immunostimulants, other alimentary tract and metabolism products. - 10% to 20% of patients: cardiac therapy, drugs for constipation, drugs for functional gastrointestinal disorders, psycholeptics, stomatological preparations, vitamins, and anti-inflammatory and antirheumatic products, other nervous system drugs, immune sera and immunoglobulins. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
15 May 2021
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
1 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 74
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Worldwide total number of subjects |
74
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
66
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
All investigators were oncologists. | ||||||||||||
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Pre-assignment
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Screening details |
Patients who completed the CL2-95014-002 study and received clinical benefit from previous treatment with S95014 as per investigator’s judgment, were included in the current CL2-95014-003 study. Other main criteria for inclusion in the study were signed informed consent and assent (where appropriate) and highly effective contraception method. | ||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
This was a non-randomized, open-label, roll-over study of S95014 lyophilizate during the consolidation phase of pediatric patients with ALL.
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Arms
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Arm title
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Consolidation phase | ||||||||||||
Arm description |
In this study, patients were treated for the consolidation phase and received the backbone chemotherapy agents outlined in the ALL-MB 2015 protocol. The patients were assigned to receive lyophilized pegaspargase (S95014) which was administered on 9 occasions, at weeks 7, 9, 11, 15, 17, 19, 23, 25 and 27 (3 phases S1, S2 and S3) over 1-hour IV infusion, at a dose of 1000 U/m². | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Pegaspargase
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Investigational medicinal product code |
S95014
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Other name |
Oncaspar®
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
S95014 lyophilizate was reconstituted with sterile water for intravenous (IV) administration and was administered every two weeks during the consolidation phase for a total of 9 infusions, at weeks 7, 9, 11, 15, 17, 19, 23, 25 and 27, at a dose of 1000 U/m².
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Baseline characteristics reporting groups
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Reporting group title |
Consolidation phase
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Reporting group description |
In this study, patients were treated for the consolidation phase and received the backbone chemotherapy agents outlined in the ALL-MB 2015 protocol. The patients were assigned to receive lyophilized pegaspargase (S95014) which was administered on 9 occasions, at weeks 7, 9, 11, 15, 17, 19, 23, 25 and 27 (3 phases S1, S2 and S3) over 1-hour IV infusion, at a dose of 1000 U/m². | ||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Analysis Set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Safety Analysis Set (SAS) was defined as the set of all patients who had received at least one dose of S95014.
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End points reporting groups
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Reporting group title |
Consolidation phase
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Reporting group description |
In this study, patients were treated for the consolidation phase and received the backbone chemotherapy agents outlined in the ALL-MB 2015 protocol. The patients were assigned to receive lyophilized pegaspargase (S95014) which was administered on 9 occasions, at weeks 7, 9, 11, 15, 17, 19, 23, 25 and 27 (3 phases S1, S2 and S3) over 1-hour IV infusion, at a dose of 1000 U/m². | ||
Subject analysis set title |
Safety Analysis Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety Analysis Set (SAS) was defined as the set of all patients who had received at least one dose of S95014.
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End point title |
Extent of exposure [1] | |||||||||||||||
End point description |
All 74 patients received at least one dose of S95014 (1000 U/m²). A single dose was received by 7 patients, 2 doses only were received by 10 patients, and 3 doses only were received by 3 patients; Thus, 20/74 patients (27%) received 3 doses or less. Except for 2 patients who received 8 doses, the remaining patients (52/74 [70%]) received 9 doses, as per protocol.
The number of doses administered was 7.0 Mean ± 3.23 SD (median: 9).
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End point type |
Primary
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End point timeframe |
From the Inclusion visit until the last S95014 infusion.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been provided since data was summarized using descriptive statistics. |
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| No statistical analyses for this end point | ||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the Inclusion visit up until 30 days after the last S95014 infusion or the date of withdrawal, whichever is earlier.
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Adverse event reporting additional description |
Treatment-emergent adverse event (TEAE) was defined as any untoward medical occurrence in a patient who received the IMP. The serious TEAEs include those upgraded by the Sponsor. No new safety concerns for S95014 were detected and it was well tolerated. No fatal events were reported during the study.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Consolidation phase
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Not applicable | |||
