Clinical Trials /

A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents

NCT02716233

Description:

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. 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. 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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
  • Official Title: A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents

Clinical Trial IDs

  • ORG STUDY ID: AOM10205
  • NCT ID: NCT02716233

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
pegaspargase 1250 IU/m2 x 2ONCASPAR 1250 IU/m2 x 2Arm 2
pegaspargase 2500 IU/m2 x 1ONCASPAR 2500 IU/m2 x 1Arm 1

Purpose

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. 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. 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 Arms

NameTypeDescriptionInterventions
Arm 1Active Comparatorpegaspargase 2500 IU/m2 x 1: infusion of a conventional dose of pegaspargase during induction therapy: 2500 IU/m2x1
  • pegaspargase 2500 IU/m2 x 1
Arm 2Experimentalpegaspargase 1250 IU/m2 x 2: fractionation of the 2500 IU/m2 pegaspargase dose in two infusions of 1250 IU/m2 each
  • pegaspargase 1250 IU/m2 x 2

Eligibility Criteria

        Inclusion Criteria:

          -  ALL L1 or L2

          -  B-lineage or T- lineage ALL

        Exclusion Criteria:

          -  L3 (Burkitt's leukemia)

          -  Mixed Phenotype Acute Leukemia (WHO criteria).

          -  Infant ALL (age ≤ 365 days)

          -  Philadelphia (Ph)+/Breakpoint Cluster region (BCR)-Abelson (ABL) ALL
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy
Time Frame:Day 33
Safety Issue:
Description:asparaginase activity > 100 IU/L

Secondary Outcome Measures

Measure:Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L
Time Frame:Day 33 of induction
Safety Issue:
Description:
Measure:Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy
Time Frame:Day 40 of induction
Safety Issue:
Description:
Measure:Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L
Time Frame:Day 40 of induction
Safety Issue:
Description:
Measure:Incidence of antibodies against asparaginase, measured in serum
Time Frame:Day 4 of delayed intensification
Safety Issue:
Description:
Measure:Incidence of silent inactivation
Time Frame:First 6-9 months
Safety Issue:
Description:Silent inactivation or subclinical hypersensitivity is defined as a plasma PEGasparaginase activity level <100 IU/L at day 7+/- 1 or <20 IU/L at day 14 +/- 11 after administration in a patient without clinical symptoms of allergy
Measure:Percentage of patients without switch to Erwinia asparaginase
Time Frame:First 6-9 months
Safety Issue:
Description:
Measure:Percentage of patients receiving more than 95% of the intended dose of asparaginase
Time Frame:First 6-9 months
Safety Issue:
Description:
Measure:Morphological Complete Remission (CR) rates
Time Frame:Day 35-Day 42
Safety Issue:
Description:Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).
Measure:Minimal Residual Disease (MRD)
Time Frame:Day 35-Day 42, Day 65-Day 105
Safety Issue:
Description:MRD will be assessed by Ig/T cell receptor (TCR)-based real-time quantitative (RQ)-polymerase chain reaction (PCR), assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL). Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).
Measure:Cumulative Incidence of relapses
Time Frame:5 years
Safety Issue:
Description:Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).
Measure:Cumulative Incidence of relapse according to site of relapse
Time Frame:5 years
Safety Issue:
Description:Bone-Marrow (BM) relapses, central nervous system (CNS) relapses, gonadal relapses, combined relapses. Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).
Measure:All other adverse events related to asparaginase
Time Frame:within the first 7 weeks (Day 49) of treatment and anyway before Day 8 of consolidation
Safety Issue:
Description:Drug-induced hyperglycemia or diabetes, coagulopathy, allergy Non CNS thrombosis Grade 1-2 Adverse Events (AE): pancreatitis, hyperbilirubinemia
Measure:Late adverse events related to asparaginase
Time Frame:after Day 49 of induction or anyway at Day 8 of consolidation or after
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Assistance Publique - Hôpitaux de Paris

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