NCT02716233

Brief Summary

A still major question in the field of acute lymphoblastic leukemia (ALL) in children - an extremely heterogeneous disease though curable in 80-90% of children and 70-80% of the adolescents - is the optimal use of L-asparaginase (ASNase). It is known that administering ASNase results in the depletion of asparagine circulating in the blood, which starves the leukemic cells and results in their death. But indeed the use of ASNase varies between protocols considering the different brands, the dose and the administration modalities. Oncaspar (PEGylated E. coli asparaginase, pegaspargase) was thus developed with the goal of reducing the immunogenicity of the native ASNase. This is a French prospective multicentric cohort study of children and adolescents with ALL, stratified on (i) the type of ALL ( B vs T) and (ii) the anticipated risk (stratified in 3 groups for childhood B-cell precursor (BCP)-ALL and 2 groups for T-cell ALL). It aims to answer to two different issues:

  1. 1.Randomized question: what is the best way to administer pegaspargase? A cohort of children and adolescents with standard or medium risk ALL will be randomized to receive during induction either one infusion of ONCASPAR® 2500 IU/m2 at D12 or two infusions of ONCASPAR® at 1250 IU/m2 each at D12 and D26. Patients will then receive 2500 IU/m2 or 1250 IU/m2 per dose during consolidation and delayed intensification according to the initial arm of randomization.
  2. 2.Non randomized question: In the High/Very High Risk groups, a non randomized intensification of the scheme of asparaginase administration is proposed during induction therapy: 2 infusions of 2500 IU/m2/day (D12 and D26) will be administered. All patients will receive 2500 IU/m2 per dose during consolidation and delayed intensifications.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,044

participants targeted

Target at P75+ for phase_3

Timeline
10mo left

Started Sep 2016

Longer than P75 for phase_3

Geographic Reach
1 country

28 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress92%
Sep 2016Mar 2027

First Submitted

Initial submission to the registry

February 15, 2016

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 23, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

September 19, 2016

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2022

Completed
4.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Expected
Last Updated

September 16, 2025

Status Verified

May 1, 2024

Enrollment Period

5.5 years

First QC Date

February 15, 2016

Last Update Submit

September 10, 2025

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

  • Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy

    asparaginase activity \> 100 IU/L

    Day 33

  • Incidence of directly asparaginase-related severe toxicities (Grade ≥ 3 as assessed by CTCAE v4.0) observed during induction therapy

    Incidence of severe toxicities (Grade ≥ 3) directly asparaginase-related (CNS thrombosis, pancreatitis, anaphylaxis, and hyperbilirubinemia) between Day 12 and Day 49 of treatment and anyway before Day 8 of consolidation

    Between Day 12 of induction and Day 8 of consolidation

Secondary Outcomes (13)

  • Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L

    Day 33 of induction

  • Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy

    Day 40 of induction

  • Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L

    Day 40 of induction

  • Incidence of antibodies against asparaginase, measured in serum

    Day 4 of delayed intensification

  • Incidence of silent inactivation

    First 6-9 months

  • +8 more secondary outcomes

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

pegaspargase 2500 IU/m2 x 1: infusion of a conventional dose of pegaspargase during induction therapy: 2500 IU/m2x1

Drug: pegaspargase 2500 IU/m2 x 1

Arm 2

EXPERIMENTAL

pegaspargase 1250 IU/m2 x 2: fractionation of the 2500 IU/m2 pegaspargase dose in two infusions of 1250 IU/m2 each during delayed intensification

Drug: pegaspargase 1250 IU/m2 x 2

Interventions

pegaspargase 1250 IU/m2 x 2DRUG

only for ALL of standard risk and medium risk

Also known as: ONCASPAR 1250 IU/m2 x 2
Arm 2
pegaspargase 2500 IU/m2 x 1DRUG

only for ALL of standard risk and medium risk

Also known as: ONCASPAR 2500 IU/m2 x 1
Arm 1

Eligibility Criteria

Age12 Months - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Children and adolescents Age \> 12 months but \< 18 yearsB-lineage or T- lineage ALL
  • Written informed consent obtained before day 8 of treatment
  • L3 (Burkitt's leukemia) (LMB type protocols)
  • Mixed Phenotype Acute Leukemia (WHO criteria).
  • Infant ALL (age ≤ 365 days (Interfant 06 protocol)
  • Secondary leukemia
  • Patients previously treated with chemotherapy (steroid exposed patients can be included and stratified according to Section 3.5) Known allergy to pegylated products
  • Known HIV positivity
  • CNS thrombosis during Prophase

You may not qualify if:

  • Ph+/BCR-ABL ALL (ESPhALL protocol)
  • CNS thrombosis before D12

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

CHU

Amiens, 80054, France

Location

CHU

Angers, 49033, France

Location

CHRU

Besançon, 25030, France

Location

CHU

Bordeaux, 33076, France

Location

CHU

Brest, 29609, France

Location

CHU

Caen, 14033, France

Location

CHU

Clermont-Ferrand, 63003, France

Location

CHU

Dijon, 21079, France

Location

CHU

Grenoble, 38043, France

Location

CHU

Lille, 59037, France

Location

CHU

Limoges, 87042, France

Location

Chu-Ihope

Lyon, 69373, France

Location

CHU

Marseille, 13385, France

Location

CHU

Montpellier, 34295, France

Location

CHU

Nancy, 54511, France

Location

CHU

Nantes, 44093, France

Location

CHU

Nice, 06200, France

Location

CHU Saint Louis

Paris, 75010, France

Location

CHU Armand Trousseau

Paris, 75012, France

Location

CHU Robert Debré

Paris, 75019, France

Location

CHU

Poitiers, 86000, France

Location

CHU

Reims, 51100, France

Location

CHU

Rennes, 35203, France

Location

CHU

Rouen, 76031, France

Location

CHU

Saint-Etienne, 42270, France

Location

CHU

Strasbourg, 67098, France

Location

CHU

Toulouse, 31059, France

Location

CHU

Tours, 37044, France

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

pegaspargase

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 15, 2016

First Posted

March 23, 2016

Study Start

September 19, 2016

Primary Completion

April 1, 2022

Study Completion (Estimated)

March 1, 2027

Last Updated

September 16, 2025

Record last verified: 2024-05

Locations

FR(28)