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.
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
| Drug | Synonyms | Arms |
|---|
| pegaspargase 1250 IU/m2 x 2 | ONCASPAR 1250 IU/m2 x 2 | Arm 2 |
| pegaspargase 2500 IU/m2 x 1 | ONCASPAR 2500 IU/m2 x 1 | Arm 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
| Name | Type | Description | Interventions |
|---|
| Arm 1 | Active Comparator | pegaspargase 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 2 | Experimental | pegaspargase 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 |
Last Updated
February 19, 2019
